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Norihiro KATO, Tomo KANDA, Miki SAGARA, Angelo BOS, Emilio H. MORIGUCH ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
801-809
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Although a variety of techniques have been devised to assess salt sensitivity, most have proven cumbersome from a methodological perspective. We therefore attempted to develop a 2-week method by which participants could be tested in an outpatient setting without requirement of a strict dietary regimen. In this method, subjects take 140 mEq of an NaCl supplement per day for 1 week and 25 mg of hydrochlorothiazide daily for another week while maintaining their customary diet. In our first trial, 8 healthy volunteers submitted to this method, as well as to a widely-used rapid volume expansion and contraction protocol. Blood pressure measurements, blood sampling and 24-h urine collection were performed before, in the middle of, and after each intervention. There was a fair correlation (r =0.69) between the two protocols with respect to the changes in mean blood pressure (ΔMBP), a measure of salt sensitivity. In our second trial, we tested the method on 82 Japanese subjects who had never been treated with antihypertensive drugs. ΔMBP was significantly correlated with plasma renin activity (PRA) during salt loading (r =0.52, p <0.0001) and with the changes in atrial natriuretic peptide (ΔANP) (r =-0.34, p =0.0018). When total subjects were divided into two subgroups by age, a similar tendency of correlation was observed. Age, PRA during salt loading, ΔANP, and Δnorepinephrine were proven to be significant predictors of salt sensitivity and accounted for 46% of the ΔMBP variances. Based on these results, the dietary method presented here seems to be applicable for a population-based survey. Our preliminary data also suggest that PRA and ANP would be of predictive value in the salt sensitivity test. (Hypertens Res 2002; 25: 801-809)
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Masahiko TOZAWA, Kunitoshi ISEKI, Chiho ISEKI, Saori OSHIRO, Yasushi H ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
811-816
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
A family history of hypertension, obesity, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia have all been associated with risk of hypertension. We retrospectively conducted a longitudinal study in a large screened cohort to explore the effect of the clustering of these five risk factors on the elevation of blood pressure (BP) in normotensive subjects at baseline. The study group comprised 4, 857 normotensive subjects not treated with antihypertensive drugs (systolic BP <140 mmHg, diastolic BP <90 mmHg, 3, 111 men and 1, 746 women) who were followed up from 1997 to 1999. By 1999, 360 subjects had BP at the hypertensive level (systolic BP≥140 mmHg or diastolic BP≥90 mmHg). The incidence of subjects whose BP became hypertensive was 37 per 1, 000 person-years. After adjusting for age, sex, systolic BP and other clinical factors, multiple logistic analysis showed that the relative risk of BP elevation was 1.49 (95% CI: 1.09 to 2.05) in subjects with one risk factor; 1.65 (95% CI: 1.15 to 2.27) in those with two risk factors; 1.42 (95% CI: 0.91 to 2.32) in those with three; and 4.86 (95% CI: 2.58 to 9.16) in those with four or more when compared with subjects with no risk factors. Multiple regression analysis showed that the number of risk factors was positively correlated with an increase in BP from 1997 to 1999; the regression coefficient was 0.51 (p =0.001) for increase in systolic BP, and 0.31 (p =0.008) for increase in diastolic BP after adjusting for age and sex. In conclusion, clustering of risk factors significantly predicted the development of hypertension. (Hypertens Res 2002; 25: 811-816)
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Koutaro TSUNEMI, Shinji TAKAI, Masayoshi NISHIMOTO, Atsushi YUDA, Shig ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
817-822
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Aortic aneurysm is a chronic degenerative condition associated with atherosclerosis. Recent studies have revealed that angiotensin (Ang) II plays important roles in atherosclerosis. In this study, to investigate the relationship between aortic aneurysm and Ang II, we measured the activities of the angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase-like enzyme, in human aneurysmal and control aortae. Aneurysmal aortic specimens were obtained from 16 aneurysm patients and control aortic specimens were obtained from 16 patients who underwent coronary artery bypass surgery (8 patients in each group were administered ACE inhibitors). The ACE and chymase-like enzyme activities were determined using extracts from vascular tissues. Both the ACE and chymase-like enzyme activities in the aneurysmal aortae were significantly higher than those in the control aortae (p <0.01). In the patients treated with ACE inhibitors, the ACE activity in the aneurysmal aortae tended to be low, but the chymase-like enzyme activity tended to be high. In the aneurysmal aortae, the chymase-like enzyme activity in the adventitia was significantly higher than that in the intimal or medial layers (p <0.01), while differences in ACE activity were not observed. Our results suggest that increases in local Ang II formation induced by chymase-like enzymes may play important roles in the pathogenesis of aneurysmal formation. (Hypertens Res 2002; 25: 817-822)
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Tatsuya TAGAWA, Yoshitaka HIROOKA, Hiroaki SHIMOKAWA, Kiyoshi HIRONAGA ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
823-829
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
We have previously shown that long-term treatment with eicosapentaenoic acid (EPA) improves endothelium-dependent vasodilation of the atherosclerotic arteries in both animals and humans. The aim of the present study was to examine whether EPA treatment also improves metabolic vasodilation evoked by exercise in patients with coronary artery disease (CAD). Forearm blood flow (FBF) was measured by strain gauge plethysmography in 10 patients with stable CAD, before and 3 months after oral treatment with EPA (1, 800 mg/kg). FBF was measured at rest and during intra-arterial infusion of acetylcholine or sodium nitroprusside, before and after intra-arterial infusion of N G-monomethyl-L-arginine (L-NMMA, an inhibitor of nitric oxide (NO) synthesis). A rhythmic handgrip exercise was also performed for 3 min before and after L-NMMA, and FBF was measured for 3 min just after the handgrip exercise. These protocols were repeated after the long-term treatment with EPA for 3 months. The long-term treatment with EPA significantly improved the FBF responses to acetylcholine (p <0.01), which was significantly reduced by acute administration of L-NMMA (p <0.01). By contrast, the EPA treatment did not affect the endothelium-independent responses to sodium nitroprusside. Metabolic increases in FBF caused by the handgrip exercise were not significantly decreased by L-NMMA before the EPA treatment. The EPA treatment significantly augmented the exercise-induced increases in FBF (p <0.05) and L-NMMA acutely abolished this augmentation (p <0.01). These results indicate that long-term treatment with EPA improves both endothelium-dependent and exercise-induced forearm vasodilations in patients with CAD and that NO is substantially involved in the EPA-induced improvement of the FBF responses in patients with CAD. (Hypertens Res 2002; 25: 823-829)
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Ichiei NARITA, Noriko SAITO, Shin GOTO, Arimasa SHIRASAKI, Yoshio MORI ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
831-836
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
The SA gene has been shown to be much more highly expressed in the kidneys of spontaneously hypertensive rats than in the corresponding wild-type strain. Genetic polymorphism of this gene has been shown to play a role in human hypertension, although the details of this association remain controversial. We investigated the possible associations between SA gene polymorphism and both hypertension and the prognosis of renal function in patients with immunoglobulin A nephropathy (IgAN). Genomic DNA was isolated from the peripheral blood of 367 individuals, including 274 patients with histologically proven IgAN and 100 controls without any history of renal disease. The SA genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) with Pst I. The frequencies of genotypes and alleles were not different between the patients with IgAN and those without renal disease. In the group without renal disease, the SA gene polymorphism was not associated with hypertension. However, in the patients with IgAN the A1 allele frequency was significantly higher in the hypertensives than in the normotensives. The renal survival of the patients with the A2 allele tended to be better than that of those without the A2 allele. The findings thus suggest that SA gene polymorphism may be associated with the renal prognosis of IgAN through its effect on blood pressure. Further, they suggest that the sensitivity to this gene polymorphism increases in patients with renal injury. (Hypertens Res 2002; 25: 831-836)
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Atsuhisa SATO, Matsuhiko HAYASHI, Takao SARUTA
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
837-842
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
It has been reported that treatment with an angiotensin-converting enzyme (ACE) inhibitor is not adequate to suppress aldosterone, and we previously demonstrated that adding spironolactone to an ACE inhibitor may have beneficial effects on left ventricular hypertrophy (LVH) in selected patients with essential hypertension (EH). We have extended our previous short-term study, and addressed the relative long-term clinical effects of spironolactone and an ACE inhibitor in patients with EH who have LVH. Twenty patients with EH and concomitant LVH participated in this study. Subjects were treated with either an ACE inhibitor alone (group 1: 10 patients) or an ACE inhibitor plus spironolactone at the dose of 25 mg (group 2: 10 patients) for 60 weeks. The baseline clinical and echocardiographic characteristics of the two groups were similar. Final values of blood pressure were also similar between the two groups. The LV mass index (LVMI) decreased significantly in both groups, but the extent of reduction was significantly greater in group 2 at 60 weeks. The early peak to atrial peak filling velosities ratio (E/A ratio) was significantly increased to a similar extent in both groups. Serum procollagen type III amino-terminal peptide (PIIINP) was significantly decreased in group 2, but not in group 1. In group 2, there was a statistically significant correlation between the changes in LVMI and PIIINP. In conclusion, adding spironolactone to therapy with an ACE inhibitor for 60 weeks may have beneficial effects in patients with EH and concomitant LVH. Our study strongly suggests the possibility that attenuation of the effects of cardiac aldosterone in patients with EH by treatment with spironolactone and an ACE inhibitor may become a new goal for the prevention and regression of cardiac hypertrophy. (Hypertens Res 2002; 25: 837-842)
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Shinji TAMAKI, Yasuyuki NAKAMURA, Yasuyuki TSUJITA, Akihiko NOZAKI, Ke ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
843-848
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Recent studies have described a linkage between angiotensin converting enzyme (ACE) gene polymorphism and hypertension in a large number of hypertensive sibs. Moreover, among Japanese, the DD genotype of the ACE gene has been reported to be a genetically predisposing factor for hypertension in a large general population. However, there is some controversy regarding the association between the ACE insertion/deletion (I/D) polymorphism and systemic hypertension. Therefore, we examined the influence of the ACE I/D polymorphism in a random Japanese population. The participants were 2, 892 subjects (1, 110 males: mean age, 58.4±15.5; 1, 782 females: mean age, 56.2±15.7) who underwent medical examinations in 1999 in Shigaraki, a suburban town located in an urban area in Shiga prefecture. Among them, 2, 395 subjects (917 males: mean age, 58.0±15.7; 1478 females: mean age, 56.3±15.6) who gave their informed consent for genetic analysis were enrolled in the present study. Every year since 1991, we have repeatedly performed medical examinations in Shigaraki. ACE genotypes were determined by polymerase chain reaction (PCR) methods. Logistic analysis revealed that age (p <0.001; odds ratio=1.091), body mass index (BMI) (p <0.001; odds ratio=1.211), and family history of hypertension (p <0.001; odds ratio=0.371) were associated with hypertension (systolic blood pressure greater than 140 mmHg and diastolic greater than 90 mmHg). There was no association between ACE polymorphism and blood pressure. There were also no significant differences in blood pressure among males or females across the three genotypes. Moreover, in an analysis of 1, 484 subjects (549 males: mean age, 62.8±12.1; 935 females: mean age, 61.2±12.6) who were followed-up since 1991, there was no association between ACE polymorphism and changes in blood pressure (p =0.3905). We conclude that ACE polymorphism does not appear to have any significant association with blood pressure, changes in blood pressure or sex in Japanese subjects, who have a more homogeneous genetic background than any other group reported to date. (Hypertens Res 2002; 25: 843-848)
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Satoru KURIYAMA, Haruo TOMONARI, Goro TOKUDOME, Makoto HORIGUCHI, Hiro ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
849-855
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). Both groups then received add-on therapy with an ARB (candesartan 4 mg once daily) for an additional 12 weeks. During the monotherapy period, blood pressure was decreased equally well in both groups. Daily urinary protein excretion remained unchanged in the CCB-treated group (control period, 4.0±1.8 g/day vs. CCB period, 4.1±1.9 g/day; ns; n =8), but decreased in the ACE-I-treated group (control period, 4.3±1.8 g/day vs. ACE-I period, 3.5±1.7 g/day; p <0.05; n =9). After the combined therapy period, blood pressure was decreased to the same degree in both groups. Although ARB plus CCB significantly reduced urinary protein excretion (to 3.5±1.5 g/day; p <0.05 vs. control period; n =8), a more profound reduction was achieved with ARB plus ACE-I (to 2.6±1.3 g/day; p <0.01 vs. control period; n =9). Monotherapy with the ACE-I increased the serum potassium concentration, and this elevation was sustained after addition of the ARB. In contrast, the serum potassium concentration was not influenced by monotherapy with the CCB, but was significantly increased after addition of the ARB. A decreased hematocrit was observed in the ARB plus ACE-I group. The present study suggests that combined antihypertensive therapy with either a CCB plus an ARB or an ACE-I plus an ARB exerts an antiproteinuric effect in patients with type 2 diabetic nephropathy with mildly impaired renal function. Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study. (Hypertens Res 2002; 25: 849-855)
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Kenji AMAMOTO, Tomonori OKAMURA, Shinji TAMAKI, Yoshikuni KITA, Yasuyu ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
857-864
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
In Japanese and other Asians, the prevalence of genetically decreased mitochondrial aldehyde dehydrogenase (ALDH2) activity is higher than in Caucasians. The aim of this study was to elucidate the relation between ALDH2 genotypes and blood pressure levels or hypertension in Japanese. After obtaining informed consent for genetic analysis from 917 men and 1, 478 women who lived in a mountainous farming region near Kyoto and who were free from cardiovascular disease and liver dysfunction, the authors identified the ALDH2 genotype in all subjects. Differences in blood pressure level among genotypes were then compared by analysis of covariance, and the relation between genotypes and hypertension was also analyzed by logistic regression analysis. The frequencies of genotypes *1/*1, *1/*2, and *2/*2 were 44.7%, 46.9% and 8.4% in men, and 50.1%, 43.2% and 6.8% in women, respectively. In men, systolic and diastolic blood pressures tended to decrease in the order of *1/*1>*1/*2>*2/*2. However, adjustment for confounding factors including alcohol consumption resulted in the disappearance of significance. Logistic regression analysis adjusted for the same confounding factors for men showed that the odds ratios (OR) of being hypertensive in the *2 allele to not having *2 allele were 0.67 (95% confidence interval (CI): 0.47-0.96). However, in the subgroup analyses, this relation was not observed in the group having a below-median level of alcohol consumption (OR=0.92; 95% CI: 0.53-1.62) or in the group not taking antihypertensive agents (OR=0.77; 95% CI: 0.52-1.15). Furthermore, we did not observe any relation between the ALDH2/*2 allele and hypertension in women (OR=1.07; 95% CI: 0.80-1.42). The results suggest that there may be no causal relation between hypertension and the ALDH2 genotype per se, after excluding for some confounding factors, especially for alcohol drinking. (Hypertens Res 2002; 25: 857-864)
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Hiromichi SUZUKI, Yoshihiko KANNO, Naofumi IKEDA, Hidetomo NAKAMOTO, H ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
865-873
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
The coexistence of hypertension increases cardiovascular risks and the rate of deterioration of renal function for diabetic patients. For patients with left ventricular hypertrophy (LVH), the use of an angiotensin converting enzyme (ACE) inhibitor is known to be effective and well tolerated and to be protective against chronic renal insufficiency (CRI). However, serious adverse reactions to ACE inhibitors, such as the rapid deterioration of renal function, have been reported, making physicians hesitant to use these agents. To resolve this dilemma, we compared changes in renal function and left ventricular function and the safety and effectiveness of benazepril, an ACE inhibitor, in patients with diabetic nephropathy, with or without LVH. The age, sex, duration of diabetes, levels of blood pressure and blood glucose and rates of creatinine clearance (CrCl) were compared between 36 diabetic patients with LVH and 36 matched diabetic patients without LVH. The rates of CrCl in all patients were between 14 and 35 ml/min, and all patients received an ACE inhibitor before enrollment. The group comprised 43 men and 29 women, with a mean age of 56±4 years. These patients were divided into three groups, each of which was subdivided into a group with and a group without LVH. Group I (without LVH) or I-L (with LVH) received a half dose of benazepril (2.5 mg daily), Group II (without LVH) or II-L (with LVH) received a normal daily dose of 5 mg benazepril, and Group III (without LVH) or III-L (with LVH) discontinued the administration of the ACE inhibitor. The follow-up period was 1 year and, during the study, blood pressure was maintained at less than 140/90 mmHg. If the blood pressure control was not satisfactory, benidipine, a calcium antagonist, and/or furosemide, a loop diuretic, and/or guanabenz, a central acting antihypertensive agent, were administered. In the diabetic patients with LVH, the administration of a normal dose of benazepril inhibited the decline of renal function and cardiac function (CrCl: 24.2±1.5 to 22.0±2.5 ml/min; EF (ejection fraction): 56±3 to 54±6%) compared to the other two groups. In patients without LVH, a half dose of benazepril preserved renal function (23.4±2.6 to 22.0±3.1 ml/min; EF: 54±3 to 56±3%). Discontinuation of the administration of ACE inhibitor led to the further progression of renal dysfunction and decreases in EF in patients with or without LVH. Our results provide some indications for the use of ACE inhibitors in diabetic patients when renal dysfunction and/or cardiac hypertrophy are present. (Hypertens Res 2002; 25: 865-873)
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Ryuichi KAWAMOTO, Katsuhiko KOHARA, Yasuharu TABARA, Tetsuro MIKI
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
875-880
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE activity, with the D allele being associated with higher ACE levels than the I allele. Thus, chronic exposure to high levels of circulating and tissue ACE may well predispose to vascular wall thickening and atherosclerosis. However, the effect of the ACE gene on carotid atherosclerosis remains controversial. We investigated the association between ACE gene I/D polymorphism and risk factor-dependent augmentation of carotid arterial remodeling in subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid artery with intima-media thickness (IMT) by ultrasonography in 184 patients (mean age±SD, 67±14 years old) and studied whether any risk factor-gene interactions were associated with carotid atherosclerosis. Out of the 184 subjects, 71 had the ACE II genotype, 87 the ID genotype and 26 the DD genotype. There was no significant difference in IMT among the three ACE genotypes. In total subjects, multiple regression analysis showed that age, total-cholesterol (T-C), and HDL-cholesterol (HDL-C) were significantly associated with IMT. However, the association between risk factors and IMT was genotype-specific. Systolic blood pressure (SBP) and HDL-C were significantly associated with IMT in ACE D carriers (DD+ID), but not in subjects with the ACE II genotype. Similarly, T-C was significantly associated with IMT only in subjects with the ACE II genotype. A general linear model of the interaction between the ACE genotype and the conventional risk factors showed that the SBP-ACE genotype interaction were significantly associated with IMT (F =7.915; p =0.005). This finding further supports the idea that analysis of risk factor-gene interaction could be a useful tool for deriving specific predictive information about the development of atherosclerosis. (Hypertens Res 2002; 25: 875-880)
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Kazue ITOH, Katsumi IMAI, Takashi MASUDA, Shimako ABE, Misuzu TANAKA, ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
881-886
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Insulin resistance is thought to raise blood pressure. Recently, a significant positive relationship between mean blood pressure and plasma leptin levels, but there have been no reports dealing with the relationship between blood pressure and either insulin resistance or serum leptin levels after weight loss. In the present work, we attempted to clarify the relationship between changes in blood pressure and either the serum leptin level or the insulin level in 102 moderately obese females (mean body mass index (BMI), 29.5±0.5 kg/m2; age, 47.0±0.9) during a 3 month period. No differences in age, fat-mass, homeostasis model assessment (HOMA), the summation of insulin (ΣIRI), plasma renin activity (PRA) or 24 h norepinephrine excretion (24hU-NE) were observed between the hypertensive (HT) group (n =31) and normotensive (NT) group (n =71) before weight loss, but the basal serum leptin was significantly higher in the HT (16.8±1.1 ng/ml) than in the NT group (15.2±0.8 ng/ml), after adjusting for abdominal total fat. After a 3 month weight reduction program, the total abdominal fat, serum leptin and ΣIRI significantly decreased in both groups. The systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 144/84 to 130/77 mmHg only in the HT but not in the NT group. The PRA decreased in both groups, while the 24hU-NE significantly decreased only in the HT group. The changes in the leptin level were significantly correlated with the changes in both ΣIRI and HOMA after weight loss in the two groups, respectively. Finally, a statistically significant positive correlation was observed between the changes in the leptin and the changes in the mean blood pressure (MBP) (r =0.412, p <0.05) only in the HT group. Multiple regression analysis revealed that the changes in MBP were independently associated with the changes in 24hU-NE and the changes in either ΣIRI or HOMA in all subjects. However, a statistically significant positive correlation was observed between the changes in MBP and the changes in leptin levels even after adjusting for the total abdominal fat, 24hU-NE and either ΣIRI or HOMA (both expressed as a percentage of the baseline value) in a multiple regression analysis only in the HT group. These results suggest that leptin may play a role in the pathophysiology of obese hypertension. (Hypertens Res 2002; 25: 881-886)
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Johji KATO, Kazuo KITAMURA, Tomohiko UEMURA, Kenji KUWASAKO, Toshihiro ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
887-892
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Adrenomedullin (AM) and atrial and brain natriuretic peptides (ANP and BNP) exert vasodilator and natriuretic actions and are thought to share roles in counteracting the progression of hypertension or heart failure as circulating or locally-acting hormones. However, little data is available with regard to their roles in subjects who have no apparent cardiovascular diseases. The present study was carried out to identify the factors that affect plasma levels of AM, ANP and BNP in the general population. We measured the plasma levels of AM, ANP and BNP in 184 local residents who had a scheduled regular health checkup, and compared the findings with those for other clinical parameters. Univariate analyses showed that the plasma levels of AM, ANP and BNP were significantly correlated with age. The plasma levels of ANP and BNP were also significantly correlated with systolic blood pressure (SBP) and with pulse pressure (PP), an indicator of the stiffness of the great vessels. Multivariate analyses conducted using a stepwise method revealed that age was a significant, independent variable for the plasma levels of AM, ANP and BNP. In addition, PP was a significant factor for the plasma levels of ANP and BNP, while the plasma AM was significantly associated with body mass index (BMI). Thus, the plasma levels of AM, ANP and BNP all increased in association with aging, and those of ANP and BNP increased in association with PP, suggesting possible relationships between the plasma levels and age-related changes in the cardiovascular system. (Hypertens Res 2002; 25: 887-892)
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Shin TAKIUCHI, Hiromi RAKUGI, Tohru MASUYAMA, Hiroshi IKEGAMI, Tomoko ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 6 号 p.
893-900
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Impairment of coronary flow reserve (CFR) in patients with type 2 diabetes has been generally demonstrated; however, there have been few studies investigating CFR in cases of relatively well-controlled diabetes, in distinction to the influence of hypertension. The purpose of the present study was to evaluate the influence of diabetes and hypertension upon CFR in relatively well-controlled patients. This study included 12 healthy controls (C group) and 57 patients with type 2 diabetes (DM) and/or essential hypertension who were divided into three groups as follows: patients with DM (DM group; n =24), patients with essential hypertension (HT group; n =15), and patients with both DM and essential hypertension (DM+HT group; n =18). We excluded patients with evidence of coronary artery disease and/or left ventricular hypertrophy. We performed transthoracic Doppler recording of diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery at rest and after maximal vasodilation by adenosine infusion (140 μg/kg/min for 3 min) CFR was defined as the ratio of hyperemic to averaged basal peak CFV. The CFR (2.92±0.46) of the DM group was not decreased compared to that of the C group (2.96±0.58), although the CFR of the HT (2.33±0.25) and DM+HT (2.35±0.25) groups were significantly reduced. Left ventricular mass index, relative wall thickness, and diastolic function were worse in the HT and DM+HT groups than in the C and DM groups. Subjects with concentric left ventricular remodeling had a lower CFR than those with normal left ventricular geometry. In conclusion, adequate hyperglycemic control prevented the progression of coronary microcirculatory disturbance, but concomitant hypertension attenuated the effect. (Hypertens Res 2002; 25: 893-900)
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Hiroto MATSUDA, Koichi HAYASHI, Koki ARAKAWA, Eiji KUBOTA, Masanori HO ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 6 号 p.
901-910
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
Renal afferent (AFF) and efferent arteriolar (EFF) responsiveness to angiotensin II (ANG II) in superficial and juxtamedullary nephrons in vivo remains undetermined, nor has it been clarified what role intrarenal autocrines/paracrines play in modulating the renal microvascular response. The present study characterized the responsiveness to ANG II (1-30 ng/kg/min) of AFF and EFF of canine superficial and juxtamedullary nephrons under pentobarbital anesthesia, using intravital CCD-videomicroscopy that allowed direct in vivo visualization of the renal microcirculation. Furthermore, the effect of prostaglandins (PG) and nitric oxide (NO) on ANG II-induced tone was examined. In superficial nephrons, ANG II induced a similar dose-dependent constriction of both AFF (46±5% constriction) and EFF (53±3%). In juxtamedullary arterioles, ANG II induced a dose-dependent constriction of EFF, whereas AFF responses were diminished (17±4% vs. 37±4% at 10 ng/kg/min). The PG inhibition by indomethacin enhanced the ANG II-induced constriction of juxtamedullary AFF, whereas no augmentation was observed in other arterioles. In contrast, NO inhibition by nitro-L-arginine methylester (L-NAME) enhanced the ANG II-induced constriction, with greater augmentation in juxtamedullary AFF and EFF. Finally, renal interstitial PG and nitrite/nitrate contents were greater in the medulla than the superficial cortex under basal and ANG II-stimulated conditions. Taken together, the results of the intravital CCD-videomicroscopy reveal that the renal microvascular action of ANG II had both zonal (juxtamedullary vs. superficial nephrons) and segmental (AFF vs. EFF) heterogeneity under the present experimental conditions. This heterogeneity was associated with a difference in the intrarenal production of prostaglandin E2 (PGE2) and NO; PGE2 contributed to segmental and zonal differences whereas NO was responsible for the zonal heterogeneity in arteriolar responsiveness. (Hypertens Res 2002; 25: 901-910)
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Yoshiko TAHIRA, Noboru FUKUDA, Morito ENDO, Ryo SUZUKI, Yukihiro IKEDA ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 6 号 p.
911-918
発行日: 2002年
公開日: 2003/06/30
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フリー
Transforming growth factor (TGF)-β activity is involved in several cardiovascular diseases owing to its effects on the growth of vascular smooth muscle cells and induction of extracellular matrix formation. We evaluated expression of TGF-β in cardiovascular organs from stroke-prone spontaneously hypertensive rats (SHR-SP) which show severe cardiovascular damages with the development of hypertension. Twelve-week-old Wistar-Kyoto (WKY)/Izm rats and SHR-SP/Izm were loaded with 1% salt for 4 weeks. Aorta, heart and kidney were removed and evaluated histologically by hematoxylin-eosin staining. Expression of TGF-β1 mRNA was evaluated by reverse transcription and polymerase chain reaction analysis in mRNA extracted with oligo dT-cellulose. Expression of TGF-β1 protein was evaluated by Western blot analysis and immunohistochemical study in renal cortex. Whereas expression of TGF-β1 mRNA was detected only in the heart of SHR-SP before salt loading, it was detected in the aorta, left ventricle of heart and renal cortex from both rat strains, and it was stronger in the renal cortex of SHR-SP than in the renal cortex of WKY rats. Expression of TGF-β1 protein was markedly higher in the renal cortex of SHR-SP than in the renal cortex of WKY rats after salt loading. TGF-β was localized at glomeruli and capillary arteries in the renal cortex, and immunostaining was stronger in SHR-SP than in WKY rats. Expression of TGF-β1 was increased in glomeruli and capillaries of the renal cortex with the development of hypertension in SHR-SP. These results implicate TGF-β in the renal damage observed in hypertension. (Hypertens Res 2002; 25: 911-918)
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Takayuki KAWAMURA, Kazunori YOSHIDA, Akira SUGAWARA, Makoto NAGASAKA, ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 6 号 p.
919-926
発行日: 2002年
公開日: 2003/06/30
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フリー
The aim of this study was to evaluate the effects of moderate-intensity regular exercise and/or an angiotensin converting enzyme (ACE) inhibition on tumor necrosis factor-α(TNF-α) and glucose and lipid metabolism parameters. Spontaneously hypertensive rats (SHRs) were fed a fructose-rich diet during 16 weeks of either exercise training (Ex group: 20 m/min, 0% grade, 60 min/day, 5 days/week), administration of an ACE inhibitor (TM group: temocapril, 10 mg/kg/day), or a combination of both (TM+Ex group). The systolic blood pressure was reduced exclusively in the TM and TM+Ex group. Epididymal fat pads (EPI) weighed less in the TM+Ex group than in the single-treatment (TM) group. The serum leptin level was significantly and directly correlated with the EPI weight (p <0.001). The TNF-α content per gram of EPI was the highest in the TM+Ex group. In addition, the EPI TNF-α level was negatively correlated with both the EPI weight and the serum leptin level (p <0.001, respectively). In contrast, the TNF-α level of skeletal muscles was identical among the groups. The extensor digitorum longus had a significantly higher abundance of TNF-α protein than the soleus muscle. These data indicate that the local TNF-α expression is tissue-specific, and that upregulation of TNF-α in EPI by exercise training and/or ACE inhibition may have contributed to the reduction in fat cell volume via the induction of apoptosis and/or the regulation of metabolic homeostasis. (Hypertens Res 2002; 25: 919-926)
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Toshiaki OKUMURA, Izumi HAYASHI, Tomoaki IKEZAWA, Mariko YAMANAKA, Tes ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 6 号 p.
927-938
発行日: 2002年
公開日: 2003/06/30
ジャーナル
フリー
COX-2 is an inducible cyclooxygenase (COX) that has been reported to be expressed in the macula densa and surrounding cortical thick ascending limb in normotensive rats. The present study assessed the contribution of COX-2 in three different rat models of hypertension, each characterized by a different activation of the renal renin-angiotensin system. Mean blood pressure (MBP) in the rat 2 kidney-1 clip (2K1C) model was significantly reduced with a COX-2 selective inhibitor, NS-398 (10 mg/kg, p.o., twice a day) (vehicle-administered rats (n =8): 154±6 mmHg; NS-398-administered rats (n =5): 128±10 mmHg). By contrast, a COX-1 selective inhibitor, mofezolac, did not lower MBP. Increased plasma renin activity (23±8 ng/kg/h (n =6) vs. sham operation, 2.4±0.9 ng/kg/h (n =4)) was markedly reduced to 6.8±2.7 ng/ml/h (n =5) by NS-398, but not by mofezolac. The development of 1 kidney-1 clip (1K1C) hypertension was also inhibited by NS-398 (vehicle (n =12): 133±1 mmHg; NS-398 (n =7): 122±3 mmHg) accompanied by a reduction in plasma renin activity (3.0±0.3 ng/ml/h, n =4) to 1.0±0.2 ng/ml/h (n =5). The COX-2 inhibitor increased urinary excretions in the 1K1C model, but not in the 2K1C model. In a deoxycorticosterone acetate (DOCA)-salt model, plasma renin activity was markedly suppressed to less than 0.3 ng/ml/h. The COX-2 inhibitor caused no significant changes in MBP, plasma renin activity, or urinary excretion, suggesting that COX-2 made a lesser contribution in this model. Increased expression of COX-2 mRNA and protein was observed in the kidneys of 1K1C and 2K1C rats, but not in DOCA-salt rats. These results suggest that COX-2 plays a significant role in the development of 2K1C and 1K1C renovascular hypertension, in addition to making a substantial contribution to the diuretic effect in the 1 K1C model. (Hypertens Res 2002; 25: 927-938)
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Yoshihiko KANNO, Hirokazu OKADA, Kenshi MORIWAKI, Shizuko NAGAO, Hisah ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 6 号 p.
939-943
発行日: 2002年
公開日: 2003/06/30
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フリー
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder in humans. Hypertension is one of the major complications, and its control might affect the renal survival and disease mortality. Suitable antihypertensive agents have been discussed based on clinical and animal studies, but no definitive conclusion has been reached. Generally, therefore, all antihypertensives are indiscriminately treated as if providing the same level of blood pressure control. In this study, the blood pressure control of two antihypertensives was investigated using a rat model of ADPKD in humans. Twenty-four male Hannover-Sprague Dawley (Han:SPRD) rats were divided into three groups: a group receiving amlodipine (6 mg/day), a group receiving benazepril (6 mg/day) and an untreated control group. Blood pressure, body weight, and urinary protein excretion were regularly measured up to week 52. Amlodipine and benazepril significantly decreased blood pressure and urinary protein excretion to the same degree. Moreover, a remarkably prolonged survival rate was observed in both groups (at week 52, the survival rate was 25% in controls, 50% in the amlodipine group, and 50% in the benazepril group). Examination at autopsy revealed that enlarged cysts were prevalent in the renal tissue of both experimental all three groups, suggesting that the cystic disease had reached the end-stage in all the animals. In conclusion, both amlodipine and benazepril significantly improved blood pressure control, urinary protein excretion, and survival rate, possibly due to their enhancement of renal survival. (Hypertens Res 2002; 25: 939-943)
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