-
Yoshihito HAYASHI, Shigeyuki SAITOH, Satoru TAKAGI, Kazufumi TUCHIHASH ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
655-660
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
In recent years, many growth factors and cytokines have been shown to be related to arteriosclerosis, and hepatocyte growth factor (HGF) has been reported to be associated with hypertension. In the present study, we investigated the relationship between HGF and hypertension by measuring the serum HGF concentration and performing 24-h ambulatory blood pressure monitoring (ABPM) in 47 randomly selected male and female subjects who underwent a medical examination for cardiovascular disease. The results were as follows. 1) The mean serum HGF concentration in the subjects was 0.35±0.14 ng/ml. 2) The serum HGF concentration was positively correlated with both the nighttime systolic and diastolic blood pressures (r =0.42, p <0.05 and r =0.47, p <0.01, respectively). 3) No correlation was found between serum HGF concentration and daytime systolic or diastolic blood pressure. 4) When subjects were divided into two groups based on the difference between daytime and nighttime systolic blood pressure, i.e., a group in which the difference was less than 10 mmHg and a group in which the difference was 10 mmHg or more, the HGF concentration was significantly higher in the former group (0.39±0.14 vs. 0.30±0.12 ng/ml, p <0.05); similarly, when subjects were divided into a group in which the difference between daytime and nighttime diastolic blood pressure was 5 mmHg and a group in which the difference was 5 mmHg or more, the HGF concentration was significantly higher in the former group (0.42±0.15 vs. 0.31±0.12 ng/ml, p <0.05). The results indicated that there is a relationship between blood pressure measured by ABPM and serum HGF concentration, and that this relationship might be an index of damage to blood vessels in patients with hypertension. (Hypertens Res 2002; 25: 655-660)
抄録全体を表示
-
Yoshikuni YAMAMOTO, Katsuhiko KOHARA, Yasuharu TABARA, Michiya IGASE, ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
661-667
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
Hepatocyte growth factor (HGF) has been shown to have a unique stimulating property on the endothelium as well as an anti-apoptotic action on the endothelium. Through these mechanisms, HGF has been shown to have an anti-atherogenic action in animal models. In atherosclerotic disorders, the circulating level of HGF has been shown to be increased to compensate for its decline in tissue. However, whether increased circulating HGF has any influence on the development of atherosclerosis has not been elucidated. In the present study, the association between plasma HGF concentration and the risk factor-carotid atherosclerosis relationship was evaluated. Three hundred and seventeen community-dwelling subjects participated in the study. The plasma concentration of HGF was determined by enzyme-linked immunosorbent assay (ELISA). The subjects were divided into two groups according to the plasma level of HGF: a low HGF group (n =199, plasma HGF <150 pg/ml) and a high HGF group (n =118, plasma HGF ≥150 pg/ml). Risk factors for atherosclerosis were evaluated in each subject. Carotid ultrasonography was performed to measure carotid arterial intima-media thickness (IMT) and the presence of plaque. The association between carotid IMT and risk factors was then evaluated in the two HGF groups. The regression lines between age and carotid IMT were significantly different between the low HGF and high HGF groups (F[1, 313]=5.98, p =0.015). The regression lines between systolic blood pressure and carotid IMT were also significantly different between the two HGF groups (F [1, 313]=5.17, p =0.024). A general linear model showed that the interaction between age and plasma level of HGF was significantly associated with carotid IMT, suggesting that the plasma level of HGF modifies the age-related increase in carotid IMT. In addition, clustering of risk factors was evaluated in subjects with carotid atherosclerosis. The number of total risk factors in carotid atherosclerosis subjects with high plasma HGF was significantly greater than that in those with low HGF, even though the two groups had a similar magnitude of carotid atherosclerosis. In conclusion, these findings indicate that risk factor-dependent augmentation of carotid atherosclerosis could be influenced by circulating HGF. (Hypertens Res 2002; 25: 661-667)
抄録全体を表示
-
Makoto SUZUKI, Mareomi HAMADA, Kozo YAMAMOTO, Yukio KAZATANI, Kunio HI ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
669-676
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
We examined the effects of aging and hypertensive left ventricular hypertrophy on the plasma level of brain natriuretic peptide (BNP), and assessed BNP as a risk marker for incident hypertensive cardiovascular events. One hundred and eighty-five hypertensive patients were echocardiographically divided into a hypertensive group with normal left ventricular mass (n =96; age range, 37-86 years; left ventricular mass, 97±14 g/m2) and a hypertensive group with left ventricular hypertrophy (n =89; 37-90 years; 140±20 g/m2). Forty-four normotensive subjects served as the normotensive group (32-84 years; 91±15 g/m2). We examined the association of age with BNP in the three groups and also evaluated BNP as a risk marker for incident cardiovascular events by following up all patients for 40 months. All three groups demonstrated a significant positive relationship between age and BNP. The slope of the relation between age and BNP was steepest in the hypertensive group with left ventricular hypertrophy (p <0.0001 vs. the other two groups). Multiple regression analysis revealed that age, pulse pressure and left ventricular mass index were significantly associated with the increase in BNP. Multivariate Cox proportional hazards regression analysis, which was used to assess the potential association of age, pulse pressure, left ventricular mass index and BNP with the cardiovascular events during follow-up, revealed the highest correlation between BNP and incident cardiovascular events (risk ratio=1.011; p =0.0011). BNP, which is synergistically increased with aging and left ventricular hypertrophy, may be an important risk marker for hypertensive cardiovascular events. (Hypertens Res 2002; 25: 669-676)
抄録全体を表示
-
Shuichi TAKAGI, Naoharu IWAI, Ryoko YAMAUCHI, Sunao KOJIMA, Shinji YAS ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
677-681
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
In epidemiological studies, moderate alcohol consumption has been consistently associated with a reduced risk of myocardial infarction (MI). About half of Japanese show an extremely high sensitivity to alcohol (ethanol), which is due to a missense mutation from glutamic acid (Glu) to lysine (Lys) at codon 487 in an isoenzyme of aldehyde dehydrogenase (ALDH2) with a low Km. We obtained a preliminary result that subjects homozygous for the Lys 487 allele had higher risk for myocardial infarction. The purpose of the present study was to assess this hypothesis by employing a larger cohort of subjects with MI. The experimental group consisted of 342 male subjects with demonstrated MI who were selected randomly from our outpatient clinic. As controls, we employed 1, 820 male subjects with no cardiovascular complications who were selected from the Suita Study. All subjects provided their written informed consent to participate in the genetic analyses. Subjects with MI were older and had higher body mass index, higher prevalence of diabetes mellitus, higher prevalence of smoking habit, higher prevalence of the Lys/Lys genotype (homozygous for Lys 487 allele), and lower high density lipoprotein (HDL) cholesterol level (HDL-C). The ALDH2 genotype affected the level of alcohol consumption, and HDL-C. Multiple logistic analyses indicated that the odds ratio of the Lys/Lys genotype to the Lys/Glu+Glu/Glu genotype was 1.56 (p =0.0359). Inclusion of HDL-C as one of the independent variables downplayed the importance of the ALDH2 genotype. This may indicate that the ALDH2 genotype affects MI via its effects on HDL-C. In conclusion, the ALDH2 Lys/Lys genotype is a risk factor for myocardial infarction in Japanese men due to its influence on HDL cholesterol level. (Hypertens Res 2002; 25: 677-681)
抄録全体を表示
-
Kazuhiro HARADA, Masami OHMORI, Akio FUJIMURA
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
683-688
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
We examined human hand veins to determine whether venoconstricting response to angiotensin II (Ang II) and noradrenaline (NA) was influenced by aging or such diseases as diabetes mellitus (DM) and hypertension (HT). Twenty healthy male subjects (20-73 years), and 8 male patients with non-insulin-dependent DM and 8 male patients with essential HT were included in this study. A constant dose (50 ng/min) of Ang II or increasing dose (2-256 ng/min) of NA was infused into the dorsal hand vein and its diameter was measured using a linear variable differential transformer. The constant infusion of Ang II caused rapid desensitization or tachyphylaxis. The venoconstriction by Ang II in the 8 elderly subjects (58 to 73 years) was significantly (p <0.05) larger than that in the 8 young subjects (20 to 36 years) from 6 to 18 min after the start of the infusion (after 6 min: 63.6±11.6 (mean±SD)% vs. 39.9±20.8%, 12 min: 34.0±11.9% vs. 12.0±12.0%). However, the venoconstriction by Ang II in the patients with DM or HT was not significantly different from that in the 9 age-matched control subjects. No significant difference in venoconstrictor response to NA was observed between the young and elderly subjects, nor between the control subjects and the patients with DM or HT. These findings indicated that venoconstrictor response to Ang II might be greater in the elderly but might not be influenced by DM nor HT. (Hypertens Res 2002; 25: 683-688)
抄録全体を表示
-
Longjian LIU, Katsumi IKEDA, Dennis H SULLIVAN, Wenhua LING, Yukio YAM ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
689-695
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
The purpose of this study was to address the association between dietary protein intake and blood pressure (BP) by combining information from all epidemiological studies that presented quantitative estimates of dietary protein intake and BP assessment. A literature search of MEDLINE, restricted to human studies on dietary protein intake and BP, was conducted. References cited in related studies were also reviewed. The results were as follows. 1) Of eleven cross-sectional studies identified, nine were suitable for quantitative pooled analysis. In men (total sample, n =19, 954 for SBP, and 19, 982 for DBP), the pooled regression coefficients (βs) of SBP and DBP on dietary protein intake were -0.03 (0.001) and -0.025 (0.01) (both, p <0.01). In women (n =950), the pooled βs were -0.014 (0.01) for SBP (p <0.05) and -0.021 (0.00) for DBP (p <0.01). In the studies that reported data for both sexes (n =12, 716 for SBP and 12, 508 for DBP), the pooled βs were -0.029 (0.01) and -0.0156 (0.00) for SBP and DBP (both p <0.01). 2) Twenty-four-hour dietary recall and 24-h urine collection were the main methods used for diet assessment, and their pooled results were consistent with the combined results for both sexes. 3) Results from two longitudinal studies showed inverse associations between dietary protein intake and BP after 3 and 7 years’ follow-up. In conclusion, a convincing cross-sectional inverse association between dietary protein intake and BP was demonstrated by the meta-analysis of nine population-based studies. The evidence from longitudinal epidemiological studies was limited. Further studies will be needed to confirm the hypothesis of the inverse dietary protein-BP association. (Hypertens Res 2002; 25: 689-695)
抄録全体を表示
-
Michinobu NAGAO, Kenya MURASE, Hideyuki SAEKI, Teruhito MOCHIZUKI, Shi ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
697-702
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
Arterial compliance is associated with the first stage of hypertension and atherosclerosis. We propose here a compliance index, which measures pulsating renal blood flow distribution using a power Doppler ultrasound (US). We assessed the relationship between the compliance index and blood pressure and between the compliance index and risk factors of atherosclerosis. The subjects consisted of 136 consecutive patients (96 males, 40 females) who underwent a physical checkup. Ages ranged from 40 to 60 years with a mean of 50.1 years. Patients with past renal disease and/or renal dysfunction were excluded. Using a power Doppler US combined with an ECG-gated and echo-tracking system, we recorded the vascular distribution of the renal parenchyma at 8 to 10 time points during an interval of the R wave of the ECG. Using a color pixel counting technique, we calculated the area (A) corresponding to the colored vascular distribution at power Doppler US. The relationships between A and the time points (t) were fitted to a quadratic equation. The compliance index of renal parenchymal vessels was obtained by twice differentiating the quadratic equation obtained above (d2A/dt2), and taking the result as a new hemodynamic index. In the univariate correlation analysis, the compliance index was correlated with age (r =-0.26, p =0.002), systolic blood pressure (r =-0.33, p =0.0001), diastolic blood pressure (r =-0.45, p <0.0001), serum uric acid (r =-0.28, p =0.001), and body mass index (r =-0.32, p =0.0002). On the multivariate stepwise regression analysis, the compliance index was significantly correlated with diastolic blood pressure (β =-0.36, p <0.0001) and body mass index (β =-0.18, p <0.0001). In conclusion, the compliance index is a candidate for a new hemodynamic marker of renal blood flow abnormality caused by hypertension. (Hypertens Res 2002; 25: 697-702)
抄録全体を表示
-
Kotaro YASUMOTO, Masanobu TAKATA, Hitoshi UENO, Fumihiro TOMODA, Hiros ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
703-710
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
To investigate whether circulating blood volume contributes to left ventricular (LV) geometry, 60 outpatients with untreated, mild to moderate essential hypertension and 45 normotensives were studied. Based on echocardiographic LV mass index and relative wall thickness, four patterns of LV geometry, i.e., normal left ventricle, concentric remodeling, eccentric hypertrophy and concentric hypertrophy, were identified. Plasma volume and blood volume were measured by the 131I labeled human serum albumin technique. LV end-diastolic volume was greater in patients with eccentric hypertrophy than in the groups of patients with normal left ventricles, concentric remodeling, or concentric hypertrophy or in normotensive subjects. No differences were found in systolic function among the five groups. Both plasma volume and blood volume were decreased in the concentric remodeling group as compared with the other four groups. However, there were no differences in plasma volume or blood volume among the normal left ventricle, eccentric hypertrophy and concentric hypertrophy groups. These data indicate that a small LV chamber in cases of “concentric remodeling” may be related to decreased plasma and blood volumes, but an enlarged LV chamber in cases of “eccentric hypertrophy” is not likely to be related to either plasma or blood volume levels in mild to moderate untreated essential hypertension. (Hypertens Res 2002; 25: 703-710)
抄録全体を表示
-
Katsushi MISAWA, Yutaka NITTA, Takao MATSUBARA, Kotaro OE, Masaru KIYA ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
711-716
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
We studied twelve patients with hypertensive left ventricular hypertrophy (LVH), 10 patients with hypertrophic cardiomyopathy (HCM) and 10 control subjects to examine the differences in coronary blood flow (CBF) dynamics between patients with hypertensive LVH and those with HCM. All subjects had normal coronary arteriograms. Measurements of CBF using Doppler Flo-Wire were performed at rest, and after infusions of acetylcholine and papaverine. The baseline CBF was significantly increased in both hypertensive LVH patients and HCM patients compared to that noted in control subjects (64.1±36.9, 80.0±38.1, 32.3±8.0 ml/min, respectively, p <0.01). Coronary flow reserve and endothelium-dependent vasodilatation were significantly lower in hypertensive LVH patients and HCM patients than in control subjects, but there was no significant difference between the hypertensive LVH and HCM patients themselves. In contrast, the diastolic/systolic velocity ratio at baseline was significantly lower in hypertensive LVH patients than in HCM patients (1.53±0.40, 6.31±7.50, p <0.05). Although CBF and coronary flow reserve correlated positively and negatively, respectively, with left ventricular mass index (r =0.51, -0.59, respectively), the diastolic/systolic velocity ratio at baseline did not show a significant correlation to left ventricular mass index. In conclusion, the diastolic/systolic velocity ratio differed between hypertensive LVH and HCM patients, independent of left ventricular mass. These results suggest that the difference of phasic pattern of CBF may be essential for coronary circulation in patients with hypertensive LVH and in those with HCM. (Hypertens Res 2002; 25: 711-716)
抄録全体を表示
-
Yasutaka YAMAMOTO, Kazuhiko SONOYAMA, Koichi MATSUBARA, Masako FURUSE, ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
717-725
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
To evaluate the current status of the management of hypertensive patients in Japan, we investigated 907 treated hypertensive patients (486 females and 421 males; mean age, 66.7 years) followed by cardiologists. According to the guidelines for the management of hypertensive patients in Japan in 2000 (JSH-2000), only 41.5% of the subjects achieved the target blood pressure, with a mean systolic blood pressure of 140.0±14.9 mmHg and a mean diastolic blood pressure of 80.0±10.7 mmHg. There were no differences between patients with and without concurrent disease or among age groups (<60, 60-69, 70-79, and 80 years and over) in systolic blood pressure levels achieved. However, the diastolic blood pressure decreased with age, indicating an increase of the pulse pressure. Overall, the prescription rates were: calcium channel blockers (CCBs), 73.0%; angiotensin converting enzyme inhibitors (ACE-inhibitors), 31.3%; angiotensin receptor blockers (ARBs), 18.9%; β-blockers, 16.2%; and diuretics, 10.1%. Although some selection of antihypertensive drugs was based on evidence from previous trials on hypertensive patients with diabetes mellitus, chronic heart failure and renal insufficiency, overall, CCBs were selected in all age groups and in all comorbid conditions. In conclusion, Japanese cardiologists do not appear to consider age and comorbidity when choosing antihypertensive managements. Based on current evidence, the management of hypertension should be individualized, with the blood pressure target level and antihypertensive medications chosen on the basis of age and comorbidity. (Hypertens Res 2002; 25: 717-725)
抄録全体を表示
-
Koh ONO, Toshifumi MANNAMI, Shunroku BABA, Hitonobu TOMOIKE, Sin-ichi ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
727-730
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
We conducted an association study between genetic variants of C-type natriuretic peptide gene (CNP) and hypertension in a Japanese population. We found four genetic variants, two in the promoter region, one missense mutation, and one in the 3′-untranslated region (3′-UTR), and genotyped all four variants in 2, 006 subjects recruited from the Suita study. One of the variants, G2628A in 3′-UTR, was found to be associated with blood pressure. Multiple logistic analyses indicated that the genotype of the G2628A polymorphism (GG=1, GA+AA=2) (p =0.0034), sex (p =0.0288), alcohol consumption (p =0.0002), age (p <0.0001), and body mass index (p <0.0001) were predictors of hypertension. The odds ratio of the GA+AA genotype over the GG genotype for hypertension was 1.40 (p =0.0034, 95% confidence interval (CI) 1.12-1.75). Multiple logistic analyses in a younger subpopulation aged below 65 years indicated that the odds ratio of the GA+AA genotype over the GG genotype for hypertension was 1.58 (p =0.0024, 95%CI 1.18-2.12). Thus, the CNP G2628A polymorphism made an even greater contribution to hypertension in the younger subpopulation. (Hypertens Res 2002; 25: 727-730)
抄録全体を表示
-
Kunitoshi ISEKI, Chiho ISEKI, Kazue ITOH, Keiko UEZONO, Miho SANEFUJI, ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
731-736
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2, 411 subjects (1, 554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension. (Hypertens Res 2002; 25: 731-736)
抄録全体を表示
-
Hiroshi TAKAKUWA, Kazuaki SHIMIZU, Yoshiaki IZUMIYA, Tamayo KATO, Izay ...
原稿種別: Original Article
専門分野: Clinical studies
2002 年 25 巻 5 号 p.
737-742
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39±2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these “non-dippers” underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling’s pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as Δpulse interval/ΔSBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187±8 to 46±8 mmol/day, and body weight decreased from 57.9±2.1 to 56.6±1.9 kg. Nighttime BP significantly decreased with dietary modification from 154±7/88±4 to 140±6/78±4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction. (Hypertens Res 2002; 25: 737-742)
抄録全体を表示
-
Eishin SHIMIZU, Mitsumasa OHYANAGI, Motomaru MASUTANI, Tadaaki IWASAKI
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
743-749
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
We investigated the concentration of stimulatory GTP-binding protein (Gs protein) in the peripheral resistance arteries of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and renovascular hypertensive rats (RHR). Changes in the function of Gs protein in SHR and WKY were also investigated by microcannulation techniques. The localization and abundance of Gs protein were determined immunohistochemically in 4-, 10- and 20-week-old SHR and age-matched WKY (control), as well as in RHR. Sections of the cremaster artery were stained with polyclonal antibodies to Gs protein. The concentration of Gs protein-like immunoreactivity in the cremaster artery was significantly lower in SHR at 4, 10, and 20 weeks of age, relative to that in age-matched WKY. In contrast, no significant differences were detected in the abundance of Gs between RHR and control rats. The dilatory response by isoproterenol in the presence of β1-adrenoceptor blocker was lower in 4- and 10-week-old SHR than in age-matched WKY. The dilatory response by cholera toxin was also lower in SHR than in WKY for these two age groups. These results indicated that the amount and function of Gs protein in the peripheral resistance vessels in SHR was reduced. Since this change occurred before the onset of hypertension and no changes were seen in the secondary hypertensive rats, this change was not a secondary change due to hypertension. The impaired receptor-Gs protein-mediated signal transduction in the peripheral resistance arteries may be one of the possible mechanisms responsible for the pathogenesis of hypertension in SHR. (Hypertens Res 2002; 25: 743-749)
抄録全体を表示
-
Masuhisa NAKAMURA, Mitsuru NOTOYA, Yuka KOHDA, Junji YAMASHITA, Yuko T ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
751-755
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
Efonidipine, a calcium antagonist, has been reported to dilate not only afferent but also efferent arterioles, thereby reducing glomerular hydrostatic pressure. We investigated the effect of chronic treatment with efonidipine or lisinopril on the afferent and efferent arteriolar diameters by the vascular cast technique. Four-week-old spontaneously hypertensive rats (SHR) were divided into three groups: untreated, efonidipine (25 mg/kg/day)-treated, and lisinopril (3 mg/kg/day)-treated. At 22 weeks of age, the renal vasculatures were fixed at the maximally dilated condition. The morphometrical measurements showed that the treatments with efonidipine and lisinopril caused structural alteration of the vasculature, resulting in significantly greater efferent arteriolar diameters than in untreated SHR. In addition, lisinopril-treated rats had wider afferent lumina. The renoprotective effect of efonidipine and lisinopril might be partly due to the structurally larger efferent arteriolar lumen. (Hypertens Res 2002; 25: 751-755)
抄録全体を表示
-
Peng LI, Peng-Ming CHEN, Shi-Wen WANG, Lan-Ying CHEN
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
757-762
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
The role of a dual angiotensin (Ang) II-forming pathway from the local renin angiotensin system (RAS) of the cardiac tissue was determined in a hamster model of cardiac hypertrophy. Time-dependent expressions of chymase and angiotensin converting enzyme (ACE) genes and their enzymes activities, and Ang II levels were measured in the hamster heart at 3 days, and at 4 and 8 weeks after pressure overload. Cardiac hypertrophy was induced by an operation to constrict the abdominal aorta. Compared to the sham-operated group, the cardiomyocyte diameters of hamster hearts at 3 days after overload underwent no obvious changes, while those at 4 and 8 weeks after overload increased markedly (p <0.01), and both transcriptional expressions of chymase and ACE genes gradually increased in the hamster hearts at 3 days, and at 4 and 8 weeks after overload, but the transcriptional expressions of angiotensin II type 1 receptor (AT1R) gene gradually decreased. Chymase and ACE activities (U/mg) (0.441±0.040 vs. 0.175±0.014, 0.446±0.036 vs. 0.160±0.016 and 0.522±0.014 vs. 0.148±0.038) (p <0.01) and (0.142±0.023 vs. 0.056±0.038, 0.317±0.017 vs. 0.079±0.016 and 0.466±0.010 vs. 0.098±0.003) (p <0.01), respectively and Ang II levels (pg/g) (98.7±4.5 vs. 71.2±4.9, 134.4±7.8 vs. 71.9±12.8 and 151.6±10.1 vs. 80.7±3.0) gradually increased in the hamster hearts, vs. sham treatment, respectively, at 3 days, and at 4 and 8 weeks after overload. However, the increases in chymase and ACE activities were much higher than those in their respective mRNA levels, and the levels of chymase activities were also higher than those of ACE activities during the development of cardiac hypertrophy. The results suggested that the increase in Ang II levels via the dual pathway of Ang II formation by chymase and ACE plays an important role in the cardiac hypertrophy of hamsters caused by the overloaded state. Importantly, in the non-hypertrophied hamster heart in the early stage after overload (at 3 days), chymase could be activated by mechanical stress in advance of an increase in its mRNA, and the Ang II level increased significantly. (Hypertens Res 2002; 25: 757-762)
抄録全体を表示
-
Yasuhiro TERANISHI, Tsutomu KUMAZAKI, Narimasa MIHO, Hiroshi SUGINO, H ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
763-771
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
Sympathetic nerve activity (SNA) was estimated by the magnitude of depressor response after ganglionic blockade with hexamethonium bromide (C6; 25 mg/kg weight). The depressor effects of C6 were significantly less in borderline-hypertensive Hiroshima rats (BHR) than in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (DOCA rats) or in spontaneously hypertensive rats (SHR), but they were not different in BHR and normotensive control Wistar rats (NCR). After sympatho-inhibition, the depressor effects of a selective vasopressin V1 receptor antagonist (V1A; 10 μg/kg: [d(CH2)51, O-Me-Tyr2, Arg8]-vasopressin) were significantly greater in BHR than in DOCA rats, SHR or NCR. In a previous study, we reported that the depressor effects of C6 were significantly less in BHR than in SHR, but after sympatho-inhibition, the depressor effects of V1A were significantly greater in BHR than in SHR (Hypertens Res 2002; 25: 241-248). After high-salt diet loading in the present study (8% salt-containing diet for 10 weeks), the magnitudes of increase in mean arterial pressure in BHR and NCR were almost the same. There was almost no difference in the depressor effects of V1A after sympatho-inhibition between BHR with high-salt intake and BHR without high-salt intake. The depressor effects of an angiotensin-converting enzyme inhibitor, captopril (1 mg/kg), were almost the same between BHR and NCR both before and after sympatho-inhibition. However, these effects were completely inhibited after the high-salt diet. The results show that SNA was within the normal range in BHR and that no further accelerated responsiveness of endogenous vasopressin was observed in BHR after high-salt intake. (Hypertens Res 2002; 25: 763-771)
抄録全体を表示
-
Etsu SUZUKI, Hiroaki NISHIMATSU, Daisuke NAGATA, Hiroshi SATONAKA, Ats ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
773-778
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
In an attempt to find a strategy to modulate the proliferation of vascular endothelial cells, we examined whether constitutive activation of proto-oncogen protein p21 (Ras) induced the reentry of confluent human umbilical vascular endothelial cells (HUVECs) into the S phase. When an adenovirus construct expressing a constitutively active Ras mutant (Ad/RasG12V) was infected into HUVECs, their morphology changed strikingly and they appeared to be transformed. However, Ad/RasG12V-infected HUVECs did not enter the S phase, as determined by assessing 3H-thymidine incorporation. In accordance with the above results, the expression of cyclin A both at the transcript and protein levels did not increase in Ad/RasG12V-infected HU VECs relative to that in control cells, although the expression of cyclin D1 was induced in Ad/RasG12V-infected cells. Interestingly, the expression of the cyclin-dependent kinase (CDK) inhibitor p21cip1 was remarkably increased while that of p27kip1 did not decrease in Ad/RasG12V-infected HUVECs. Furthermore, CDK2 activity was not induced in Ad/RasG12V-infected HUVECs. These results suggested that the constitutive activation of Ras promoted the reentry of confluent HUVECs in the G0 phase into the G1 phase, but not into the S phase. The results also indicated that the constitutive activation of Ras might have induced the persistent expression of p21cip1 and p27kip1, and that this induction of p21cip1 and p27kip1 expression possibly caused the cell cycle arrest at the G1 phase. (Hypertens Res 2002; 25: 773-778)
抄録全体を表示
-
Sanae HARADA, Tetsuo NAKATA, Atsuhiko OGUNI, Hidenori KIDO, Tsuguru HA ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
779-786
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
This study was designed to test the hypothesis that increased pressure itself could cause endothelial dysfunction and lead to decreased nitric oxide (NO) release, partly through effects on the tissue renin angiotensin system in hypertension. Cultured endothelial cells (ECs) isolated from the aortas of WKY rats were continuously exposed to a pressure of 150 mmHg in a CO2 incubator for 72 h using a pressure system, and the NOx (NO2 and NO3) and angiotensin II (Ang II) concentrations in the supernatant were measured. An Ang II type 1 receptor (AT1R) antagonist (losartan) and an Ang II type 2 receptor (AT2R) antagonist (PD123319) were added to the medium. The expression of AT1R and AT2R mRNAs was also examined. Pressure loading significantly decreased the NO release from ECs. Concomitant administration of losartan restored NO release to the level before the application of pressure (p <0.001). This effect of losartan was blocked by simultaneous administration of PD123319, bradykinin type 2 receptor antagonist, and NO synthase inhibitor (p <0.05). The Ang II concentration was increased by pressure and was further increased by losartan. The gene expression of AT1R was not changed by pressure, but AT2R mRNA was increased almost 2-fold. These results indicate that high pressure itself attenuates NO release from ECs, and that losartan improves NO release by activating the bradykinin system via AT2R stimulation. In addition, the increase of AT2R gene expression in ECs during exposure to pressure may compensate for the reduction of NO. (Hypertens Res 2002; 25: 779-786)
抄録全体を表示
-
Takeshi HAYASHI, Takeshi TSUJINO, Sachiyo IWATA, Hidemi NONAKA, Noriak ...
原稿種別: Original Article
専門分野: Experimental studies
2002 年 25 巻 5 号 p.
787-795
発行日: 2002年
公開日: 2003/04/26
ジャーナル
フリー
To assess the roles of polyamines (putrescine, spermidine, and spermine) and ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, in the development of salt-sensitive hypertension, we evaluated activity and expression of ODC, urinary polyamine excretion, and antizyme (endogenous ODC inhibitor protein) expression in Dahl salt-sensitive (SS) and salt-resistant (SR) rats after they were fed on a low (0.3%) or high (4%) salt diet for 4 weeks. We also examined the effects of spermidine and difluoromethylornithine (DFMO: a specific inhibitor of ODC) on the systolic blood pressure and ODC protein expression in SS rats fed a high salt diet. Renal ODC activity and urinary polyamine excretion in SS rats were lower than those in SR rats after 4 weeks treatment with a low or high salt diet. The renal ODC protein expression of SS rats was paradoxically increased as compared to the SR group. A high salt diet did not alter ODC activity but increased ODC protein only in SS rats. ODC mRNA and antizyme protein expressions were not significantly different among the four groups. Spermidine supplementation attenuated and DFMO exaggerated hypertension in SS rats fed a high salt diet. Spermidine down-regulated and DFMO up-regulated renal ODC protein in SS rats on a high salt diet. ODC activity was decreased but protein was paradoxically increased in kidneys of SS rats. ODC protein was suggested to increase in compensation for the inhibition of its activity. Impaired ODC activity and polyamine production in the kidney may exaggerate salt-sensitive hypertension in SS rats. (Hypertens Res 2002; 25: 787-795)
抄録全体を表示
