Hypertension Research
Online ISSN : 1348-4214
Print ISSN : 0916-9636
ISSN-L : 0916-9636
Volume 27 , Issue 3
March
Showing 1-10 articles out of 10 articles from the selected issue
Original Articles
Clinical studies
  • Yasuyuki NAKAMURA, Shinji TAMAKI, Yasukazu UCHIDA, Nobuyuki OHMICHI, O ...
    2004 Volume 27 Issue 3 Pages 137-140
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    To examine whether the response to the angiotensin II receptor antagonist losartan varies depending on the angiotensin converting enzyme (ACE) genotype, we prospectively studied the effect of losartan in 42 hypertensive patients (20 men, 22 women; mean age: 60.4 years). After a 4-week observation period, losartan was administered at 50 mg/day and blood pressure was measured every 2 to 4 weeks for 12 weeks. Among the 42 patients, 19, 11, and 12, respectively, had the II, ID, and DD ACE genotypes. The baseline plasma ACE activity in patients with the ID or DD genotype was significantly higher than that in patients with the II genotype (13.8±4.2 vs. 9.6±2.3 IU/l; p =0.0002). However, age, gender, baseline systolic and diastolic blood pressure (SBP/DBP), and body mass index (BMI) were not different among the groups. After 12 weeks of treatment with losartan alone, DBP in the ID+DD group was significantly higher than that in the II group (85.0±9.0 vs. 77.8±9.6 mmHg, p =0.018), while the percent reduction in DBP in the ID+DD group was significantly smaller than that in the II group (7.9±8.8 vs. 14.3±10.1%, p =0.035). Multiple regression analysis showed that the significant predictors of the DBP at 12 weeks were age (p =0.030), ACE genotype (p =0.029) and baseline DBP (p =0.0001). The ACE genotype may be a determinant of the response to losartan in hypertensive patients. (Hypertens Res 2004; 27: 137-140)
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  • Munemichi INABA, Yuichi NOGUCHI, Taro YAMAMOTO, Tomihiko IMAI, Masako ...
    2004 Volume 27 Issue 3 Pages 141-145
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    To investigate the effects of the diuretic, indapamide, on blood pressure (BP) and metabolic parameters, thirty hypertensive patients were treated with 1 mg of indapamide either every day or every other day. BP, fasting plasma glucose, lipids, serum potassium and uric acid were determined at baseline and after 3 months of a stable regimen of the drug. At the termination of the study, 48-h ambulatory blood pressure monitoring (ABPM) was performed. Three patients received only indapamide, while other patients were treated in combination with additional antihypertensive medications. Patients treated with daily indapamide showed a BP reduction from 162±2.9/85±2.4 mmHg to 134±2.4/71±2.6 mmHg (p <0.001). The BP reduction was similar in those patients receiving the drug every other day (137±3.4/71±3.6 mmHg). While plasma lipids and serum potassium did not differ significantly with the intervention, uric acid increased significantly with daily treatment and normalized with every-other-day treatment. Glycosylated hemoglobin A1c (HbA1c) was not altered (5.6±0.1% vs. 5.4±0.2%), and did not differ between patients with and without diabetes mellitus. ABPM revealed an average 24-h BP of 134±3.3/75±1.7 mmHg on days in which patients received the medication and 139±4.9/78±2.6 mmHg on the intervening day without indapamide (no significant difference). These results suggest that a low dose of indapamide given every day or every other day is effective in lowering BP and does not result in metabolic derangements. (Hypertens Res 2004; 27: 141-145)
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  • Yasuhiro HASEGAWA, Takenori YAMAGUCHI, Teruo OMAE, Mark WOODWARD, John ...
    2004 Volume 27 Issue 3 Pages 147-156
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    Controversy persists as to whether reducing the blood pressure of patients with a history of stroke leads to an increased risk of silent brain infarct (SBI) and dementia. A total of 667 patients were randomized to receive the angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg daily), with or without the diuretic indapamide (2 mg daily) or matching placebo(s). Brain CT scanning was performed annually over the mean follow-up period of 3.9 years. Active treatment reduced the blood pressure (systolic/diastolic) by 5.2/2.6 mmHg over the follow-up period. A total of 119 new SBI were detected and 92% of them were lacunar type small infarcts. The frequency of reaching the primary end-point (recurrent symptomatic stroke or new SBI) was similar in the placebo group (26.5%) and in the active treatment group (25.9%). There was no significant difference in brain atrophy indices between two groups. In the subgroup with a history of large artery infarction, 7 out of 55 patients from the placebo group developed new SBI, while none of the 40 patients from the active treatment group did so (p =0.020). The baseline diastolic blood pressure was significantly associated with the risk of new SBI (p =0.004), but the stroke subtype was not. In conclusion, blood pressure-lowering with a perindopril-based regimen did not increase the risk of SBI and brain atrophy in patients with a history of stroke. The baseline diastolic blood pressure was an independent predictor of new SBI, but the index stroke subtype did not influence the risk of SBI. (Hypertens Res 2004; 27: 147-156)
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  • Junko TAMAKI, Yuriko KIKUCHI, Katsushi YOSHITA, Toru TAKEBAYASHI, Naga ...
    2004 Volume 27 Issue 3 Pages 157-166
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    We investigate the relationship of urinary salt excretion to the stage of change to decrease salt intake in the Japanese diet. The data reported here were obtained from a baseline survey of the High-Risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study that was conducted as a non-randomized control trial at 12 worksites in Japan. A total of 6,816 subjects (5,410 male, 1,406 female) were used in 1999 and 2000 for the analysis. We used three categories of stage of change: precontemplation or contemplation (P/C), preparation (P), and action or maintenance (A/M). Urinary salt excretion was estimated from the sodium and creatinine concentrations in spot urine samples. Multivariate analysis indicated that urinary salt excretion among males was 0.3 g/day greater in the P/C stage than in the A/M stage (p <0.05). For non-obese females, urinary salt excretion in the P/C stage was 0.6 g/day greater than in the A/M stage (p <0.05). Multivariate analysis showed that diastolic blood pressure in males not taking antihypertensive agents was 1.3 mmHg lower in the P/C stage than in the A/M stage (p <0.05). A similar but statistically insignificant tendency was observed among non-obese females. A significant association was demonstrated between stage of change for dietary salt intake and urinary salt excretion for both males and non-obese females. There may be a potential application of the stage of change model for reducing dietary salt intake in a health promotion program. (Hypertens Res 2004; 27: 157-166)
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  • Yuhei KAWANO, Hitoshi ABE, Shunichi KOJIMA, Shuichi TAKISHITA, Hiroaki ...
    2004 Volume 27 Issue 3 Pages 167-172
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    Alcohol consumption causes biphasic changes in blood pressure (BP) in Asians. The aim of the present study was to investigate the effects of repeated alcohol intake on BP and sodium metabolism. Fourteen Japanese males with hypertension (37-67 years old) were examined under standardized conditions (Na intake 120 mmol/day). After 1 week of alcohol restriction, the patients consumed a control drink with dinner for 3 days, 1 ml/kg of alcohol for the next 7 days, then the control drink for 3 days. Supine BP and heart rate were measured 5 times daily, and urinary excretion of water and sodium was determined throughout the study period. Average BP decreased initially, then returned to the baseline level during the alcohol period. Evening BP decreased significantly throughout the alcohol period, although the reduction was attenuated during the late phase. Morning and afternoon BP did not change significantly, but tended to be elevated during the late phase. Heart rate increased both in the morning and evening during the alcohol period. Urine volume did not change during the early phase, but increased significantly during the late phase. Urinary sodium excretion decreased initially, but increased during the middle phase of the alcohol period. In conclusion, BP decreases initially with sodium retention, then returns to the baseline level with restoration of sodium balance during repeated alcohol intake in Japanese males with hypertension. Sodium retention during the early phase appears to be the consequence of BP reduction and may contribute to the subsequent changes in BP. (Hypertens Res 2004; 27: 167-172)
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  • Tomonori OKAMURA, Yuri MORIYAMA, Takashi KADOWAKI, Hideyuki KANDA, Hir ...
    2004 Volume 27 Issue 3 Pages 173-180
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    Pulse wave velocity (PWV) is an indicator of arterial stiffness, especially in the aorta, and a marker for vascular damage. We examined the association of brachial-ankle PWV (baPWV) with serum α-tocopherol and C-reactive protein (CRP) levels in addition to the traditional risk factors. Study subjects were 178 Japanese male workers aged 50-59 without past histories of cardiovascular diseases. The relation of baPWV with serum α-tocopherol and CRP levels was cross-sectionally analyzed after adjusting for other cardiovascular risk factors. The arithmetic mean of serum α-tocopherol was 38.9μmol/l, and the geometric mean of serum CRP was 0.47 mg/l. Multiple linear regression analysis indicated that serum CRP levels were associated with an elevation of baPWV, in addition to age, systolic blood pressure and heart rate. However, serum α-tocopherol, serum lipids (triglyceride, low and high density lipoprotein cholesterol), fasting plasma glucose, body mass index, smoking and alcohol drinking did not significantly correlate to baPWV. Multivariate-adjusted means of baPWV according to serum CRP quartile were 1,431, 1,436, 1,507 and 1,508 cm/s (p =0.033). The serum CRP level might be an important marker for arterial stiffness in Japanese middle-aged males. However, no relation was observed between α-tocopherol and baPWV. (Hypertens Res 2004; 27: 173-180)
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  • Yoshiki YUI, Tetsuya SUMIYOSHI, Kazuhisa KODAMA, Atsushi HIRAYAMA, Hir ...
    2004 Volume 27 Issue 3 Pages 181-191
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients. The study used a prospective, randomized, open, blinded endpoint (PROBE) design. Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease. The subjects were 1,650 outpatients aged under 75 years who had diagnoses of both hypertension and coronary artery disease. There were 828 patients subjected to intention-to-treat analysis in the nifedipine retard group and 822 patients in the angiotensin converting enzyme inhibitor group. The patients were randomized to 3 years of treatment with either nifedipine retard or angiotensin converting enzyme inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions). The primary endpoint occurred in 116 patients (14.0%) from the nifedipine retard group and 106 patients (12.9%) from the angiotensin converting enzyme inhibitor group (relative risk, 1.05; 95% confidence interval, 0.81-1.37; p =0.75). In the Kaplan-Meier estimates, there were no significant differences between the two groups (log-rank test: p =0.86). The incidence of cardiac events and mortality did not differ between the nifedipine retard and angiotensin converting enzyme inhibitor therapies. Nifedipine retard seems to be as effective as angiotensin converting enzyme inhibitors in reducing the incidence of cardiac events and mortality. (Hypertens Res 2004; 27: 181-191)
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  • Masao OMURA, Jun SAITO, Kunio YAMAGUCHI, Yukio KAKUTA, Tetsuo NISHIKAW ...
    2004 Volume 27 Issue 3 Pages 193-202
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    Secondary hypertension (SH) including endocrine hypertension has been reported to be uncommon. We estimated the prevalence of SH among hypertensive patients. We prospectively studied 1,020 hypertensive patients. As an initial screening, we measured plasma aldosterone concentration, plasma renin activity, serum cortisol concentration and plasma catecholamine concentration and conducted abdominal ultrasonography (US). As a secondary screening, we performed furosemide plus upright test, captopril renography, dexamethasone suppression test, 24-h urine catecholamine measurement and abdominal CT. Finally, primary aldosteronism with the exception of idiopathic hyperaldosteronism, pheochromocytoma, and Cushing’s syndrome were diagnosed by histopathological examination of surgical specimens. Idiopathic hyperaldosteronism was clinically diagnosed by adrenocorticotrophic hormone (ACTH)-stimulated adrenal venous sampling and renovascular hypertension by renal arteriography. There were 61 patients with primary aldosteronism, 5 with renovascular hypertension, 11 with Cushing’s syndrome, 10 with preclinical Cushing’s syndrome and 6 with pheochromocytoma, and the prevalence of SH was 9.1% among 1,020 hypertensive patients. In 76 (82%) of 93 patients with SH, hypertension was cured or improved after unilateral adrenalectomy, transsphenoidal pituitary adenectomy or percutaneous transluminal angioplasty. With the exception of US and CT, all initial and secondary screening tests were found to be sensitive and specific for differentiating SH from essential hypertension (EH). In conclusion, the measurement of various hormone concentrations was very sensitive for ruling out SH—a condition for which, in the present study, there were few specific signs or symptoms—while CT and US examinations were not always useful for differentiating SH from EH. The prevalence of curable SH among hypertensive subjects was higher in this study, which was conducted by our simple method of screening tests, than in previous reports. Hypertensive patients should be screened for SH and the underlying disease treated appropriately to avoid long-term use of antihypertensive drugs and risks of atherosclerotic complications. (Hypertens Res 2004; 27: 193-202)
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Experimental studies
  • Myriam MOUJAHIDINE, Raphaelle LAMBERT, Julie DUTIL, Ana PALIJAN, Zsuzs ...
    2004 Volume 27 Issue 3 Pages 203-212
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    Chromosomes (Chr) 10 and 16 of the Dahl salt-sensitive (S) rat harbor quantitative trait loci (QTLs) for blood pressure (BP). To facilitate gene discovery of these QTLs, gene profiling based on microarrays was combined with fine QTL mapping to identify potential candidate genes that are differentially expressed. First, the region harboring the BP QTL on Chr 16 was narrowed by comparative congenic mapping. In this endeavor, a number of new chromosome markers were generated and used to physically define the chromosome interval in question. Second, in an effort to minimize the costs of gene profiling without sacrificing the chance of gene discovery, a combination congenic strain was produced by replacing one segment of Chr 10 along with one segment of Chr 16 of the hypertensive S rat by those of the normotensive Lewis (LEW) rat. Both of these regions are known to contain BP QTLs. Third, kidneys of this combination congenic strain and the S strain were employed for expression profiling studies. Finally, a comparison between the two strains yielded a number of potentially differentially expressed candidates. Six Established Sequence Tags (ESTs) /genes among them were located in Chr 10 regions and 1 was found in a Chr 16 region, and the genetic make-ups of all these regions were shown to be different between S and LEW. However, none of these ESTs/genes identified by gene profiling were located in an interval containing a QTL. Thus, the present study highlights the importance of correlating the results of gene expression profiling with fine congenic mapping. (Hypertens Res 2004; 27: 203-212)
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  • Shinji TAKAI, Denan JIN, Masato SAKAGUCHI, Mizuo MIYAZAKI
    2004 Volume 27 Issue 3 Pages 213-219
    Published: 2004
    Released: October 19, 2004
    JOURNALS FREE ACCESS
    To clarify the mechanisms by which angiotensin-converting enzyme (ACE) inhibitors lower blood pressure or inhibit cardiac hypertrophy, we analyzed the correlations among tissue ACE activities, blood pressure and cardiac hypertrophy. In spontaneously hypertensive rats (SHR), blood pressure, heart weight and ACE activities in plasma and various tissues were measured 3, 24 and 48 h after repeated daily treatment for 2 weeks with the ACE inhibitors trandolapril, perindopril, temocapril and enalapril. For all four ACE inhibitors, blood pressure and ACE activities in the plasma, aorta and kidney were significantly reduced 3 h after the last treatment. Although hypotensive effects were maintained at 24 h, ACE activities in plasma were not suppressed by temocapril and enalapril. Even at 3 h, enalapril could not suppress ACE activity in the brain, and temocapril and enalapril could not inhibit ACE activities in the heart. Significant correlations between ACE activity in the aorta and blood pressure were observed for all four ACE inhibitors, while the ACE activities in the heart and brain were not correlated with changes in blood pressure. Significant decreases in the ratio of heart weight to body weight were observed in SHR treated with trandolapril and perindopril, whereas they were not observed with temocapril and enalapril. The ratio of heart weight to body weight was significantly correlated with ACE activity in the heart. ACE activities in vascular tissues and the heart may be important targets in terms of the ability of ACE inhibitors to lower blood pressure or inhibit cardiac hypertrophy, respectively. (Hypertens Res 2004; 27: 213-219)
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