Regular aerobic exercise training attenuates age-related reduction in central arterial compliance, an independent risk factor of cardiovascular diseases. We tested the hypothesis that even low-intensity exercise training could increase central arterial compliance in postmenopausal women. Using B-mode ultrasound, we studied the central arterial compliance of 15 postmenopausal females (age: 52-66 years) before and after a 12-week aerobic exercise intervention. Subjects performed aerobic exercise training of the same energy expenditure (cycle exercise, total 900 kcal/week, 3-5 sessions/week) at two different exercise intensities: 7 trained at low intensity (40% heart rate reserve: L-TR) and 8 trained at moderate intensity (70% heart rate reserve: M-TR). Arterial compliance increased after exercise training in the L-TR group (0.70±0.32 vs. 1.06±0.55 mm2/mmHg×10-1, p <0.05) and in the M-TR group (0.82±0.37 vs. 1.14±0.39 mm2/mmHg×10-1, p <0.05). There was no significant difference in increases of arterial compliance in either group (L-TR: 0.35±0.38 vs. M-TR: 0.32±0.33 mm2/mmHg×10-1). These results suggest that the improvement of central arterial compliance by aerobic exercise training might not be influenced by the intensity of exercise training if the energy expenditure of the training is the same. Accordingly, even low-intensity exercise training may have the effect of improving central arterial compliance. (Hypertens Res 2004; 27: 897-901)
The pathophysiology of preeclampsia (PE) remains uncertain despite many research efforts. Actual hypotheses seek to explain the vascular damage that characterizes the disease. Recently, it was reported that the mouse disrupted estrogen receptor β (ESR2) gene was associated with abnormal vascular function and hypertension. Moreover, some investigators have reported that subjects with a family history of hypertension have a statistically significant increased risk for PE. Thus, it is thought that the pathophysiology of PE overlaps that for hypertension. The aim of the present study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the human ESR2 gene and PE in Japanese subjects, and to assess the involvement of a family history of hypertension in these relationships. Based on a database search on the web site of the National Center of Biotechnology Information (NCBI), we chose four SNPs in the human ESR2 gene, and performed an association study in 84 PE patients and 160 age-matched non-PE subjects. The overall distribution in each SNP did not differ significantly between the two groups. However, after dividing the groups into subjects with and without a family history of hypertension, the allelic distribution of one of the SNPs (rs928554) revealed a positive association. Thus, a possible mutation linked to a SNP may prescribe a genetic predisposition for patients with a family history of hypertension in PE. (Hypertens Res 2004; 27: 903-909)
An abnormality in cardiovascular regulation during the prenatal period has been suggested to be the pathophysiological link between fetal growth restriction and adult hypertension. The purpose of this study was to determine how consistently abnormal the local smoothness of the very-short-term heart rate is in growth-restricted fetuses associated with severe pre-eclamptic pregnancy. Multifractal Hurst analysis on the structure function of heart rate was performed in control fetuses (n =150), in fetuses affected by severe pre-eclampsia and not showing growth restriction (n =66) and in fetuses affected by severe pre-eclampsia and showing growth restriction (n =58). The very-short-term (≤15 heart beats) generalized Hurst exponents of the order of -5 to 5 in three groups were compared. Each exponent quantifies an average local heart rate smoothness at 15-successive-heart rate sites, which were specified by the magnitude of the heart rate variation within the sites determined by and positively correlated with the order of the exponent. This means that the fetal heart rates within the sites of q ≥2 have a large fetal heart rate (FHR) variation, and those within the sites of q ≤-2 have a small FHR variation. In the fetuses affected by severe pre-eclampsia and not showing growth restriction, only values of the exponents of the order ≥2 were abnormally lower. In the fetuses affected by severe pre-eclampsia and showing growth restriction, the values of the exponents of all orders were abnormally lower. In conclusion, the local smoothness of heart rate is consistently abnormal regardless of the magnitude of heart rate variation within a very-short-term period in growth-restricted fetuses affected by severe pre-eclampsia. (Hypertens Res 2004; 27: 911-918)
Previous studies have shown that the T allele of the GNAS1 T393C polymorphism is associated with poor responsiveness to β-blockade and that the T393C polymorphism interacts with cigarette smoking and alcohol consumption in the pathogenesis of hypertension. Thus, the T393C polymorphism is likely to interact with β-adrenoceptor (β-AR) stimulation in the pathogenesis of hypertension. Although this interaction might be caused by a direct effect of Gs proteins on the cardiovascular system, it could also result from an indirect effect of Gs proteins mediated by glucose metabolism. Moreover, association studies are often irreproducible. We therefore examined the possible interaction between the T393C polymorphism and γ-glutamyl transpeptidase (GGT), which is an established biomarker of alcohol consumption, in the association with glucose metabolism as well as with hypertension in a Japanese population. Genotyping for GNAS1 was performed by using the polymerase chain reaction-restriction fragment length polymorphism method in all 821 samples. The present study showed a significant interaction between the T393C polymorphism and GGT in the association with hypertension (p =0.033). This interaction was even more significant after adjustment for all confounding factors (p =0.0025). In contrast, analysis of the possible interaction of the T393C polymorphism with GGT in the association with diabetes mellitus or fasting plasma glucose failed to show a significant result. These results did not support the hypothesis that the interaction between the T393C polymorphism and GGT in the association with hypertension could be caused by an indirect effect of Gs proteins mediated by glucose metabolism. (Hypertens Res 2004; 27: 919-924)
This study examined the relationship between arterial stiffness and autonomic nervous function in a young population. A cross-sectional study was conducted on 382 Japanese males, aged 24 to 39 years, who worked at the same information service company. Brachial-ankle pulse wave velocity (baPWV) was measured using an automatic waveform analyzer, and the spectral power of heart rate variability in the low frequency (LF: 0.04-0.15 Hz) and the high frequency (HF: 0.15-0.40 Hz) band was evaluated by the maximum entropy method. LF/HF and HF were used as the indicators of sympathetic and parasympathetic nervous activity, respectively. Psycho-hormonal responses were examined by the Profile of Mood State (tension-anxiety and anger-hostility scales) and Hamilton’s Depression Scale with serum cortisol and catecholamine levels. In a univariate analysis, baPWV was positively associated with the following variables (all p <0.05): LF/HF, age, body mass index, systolic and diastolic blood pressures, heart rate, serum total cholesterol and triglycerides, blood glucose, and plasma cortisol and noradrenaline. Multiple regression analysis indicated that LF/HF was an independent predictor of baPWV (p <0.05), after controlling for significant effects of age, systolic blood pressure, and plasma noradrenaline levels. There was no significant effect of HF on baPWV in this multivariate analysis. Neither mood state nor health-related lifestyle factors such as smoking were significant. It was suggested that baPWV is closely associated with sympathetic nervous activity in young men. (Hypertens Res 2004; 27: 925-931)
The bradykinin B2 receptor shows a protective role in the development of hypertension and renal and cardiovascular complications. It was recently reported that a polymorphism of the bradykinin B2 receptor gene (BDKRB2) is a genetic predisposing factor for hypertension and cardiovascular disease. The aim of this study was to examine the relationship of a polymorphism (-58 T/C and exon 1 +9/-9) of BDKRB2, and an insertion/deletion polymorphism (I/D) of the angiotensin converting enzyme gene (ACE) with essential hypertension and cardiovascular mortality in the Japanese population. Genotyping was carried out in 275 hypertensive and 441 normotensive subjects. Left ventricular hypertrophy (LVH) was detected by ECG in 242 untreated patients with hypertension. All participants were Japanese and gave their written informed consent. The polymorphism (-58 T/C) in the promoter region of the BDKRB2 was determined using the TaqMan-polymerase chain reaction (PCR) method, the exon 1 +9/-9 polymorphism of the BDKRB2 and I/D polymorphism of the ACE were monitored by PCR and gel electrophoresis. The genotypes and allelic frequencies were in Hardy-Weinberg equilibrium. The polymorphism (-58 T/C) in the promoter of the BDKRB2 was associated with LVH in the hypertensive group (n =242) (p =0.048; χ2 =3.9; odds ratio: 1.8; 95% confidence interval (CI): 1.0-3.3). Furthermore, the frequency of LVH in hypertensives was significantly higher in the subjects with both the BDKRB2 CC and ACE D allele than those with other genotypes (p =0.002, χ2 =9.4). However, no relationship could be found between polymorphism of the BDKRB2 (p =0.86, χ2 =0.3) or the ACE (p =0.21, χ2 =3.1) and hypertension in this group of subjects. These results suggest that the polymorphism (-58 T/C) in the promoter region of BDKRB might be a risk factor and might have a synergetic effect with the ACE for LVH in hypertensives, but it is not associated with hypertension in the Japanese population. (Hypertens Res 2004; 27: 933-938)
To assess the relationship between home blood pressure and left ventricular mass, we evaluated cardiac echocardiography in 297 hypertensive subjects (188 men and 109 women; mean age, 62.8±10.3 years) who were treated with amlodipine monotherapy over 1 year (mean dose, 5.5±2.3 mg/day). The morning hypertension group (n =57; 19.2%), who had a morning home systolic blood pressure (HSBP) ≥135 mmHg and an evening HSBP <135 mmHg, had a significantly greater left ventricular mass index (LVMI) concomitant with an increase in the homeostasis model assessment insulin resistance index (HOMA-IR) compared to the good control group (n =174; 58.6%), whose morning and evening HSBP were both <135 mmHg, and had a LVMI roughly equivalent to that of the poor control group (n =63; 21.2%), whose morning and evening HSBP were both ≥135 mmHg. By grouping of subjects according to the difference between morning and evening HSBP (ΔHSBP), subjects with a ΔHSBP≥10 mmHg had a significantly greater LVMI than subjects with a ΔHSBP <10 mmHg. Increases in LVMI in these patients were still significant after adjustment for age, gender, dose of amlodipine, alcohol consumption, body mass index, office systolic blood pressure, and morning and evening HSBP. In a stepwise multivariate regression analysis, ΔHSBP (r2 =36.2%, p <0.001), morning HSBP (r2 =5.5%, p <0.001), HOMA-IR (r2 =1.4%, p =0.016) and age (r2 =1.0%, p =0.026) were determined to be significant contributing factors for LVMI. This regression model could explain 44.1% of LVMI variability. These results suggest that morning rise in blood pressure is a dominant predictor of left ventricular hypertrophy. (Hypertens Res 2004; 27: 939-946)
Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and is thought to have antiatherosclerotic properties. Therefore, it has also been proposed that NO may be useful to regulate vascular tonus and prevent progression of atherosclerosis. On the other hand, NO activity reduces with aging. We previously reported that the plasma nitrite/nitrate (NOx: the stable end product of NO) concentration was significantly increased by intense aerobic exercise training in healthy young humans. We hypothesized that lifestyle modification (e.g., even mild regular exercise training) can increase NO production in previously sedentary older humans. We measured the plasma NOx concentration before and after a mild aerobic exercise training regimen (cycling on a leg ergometer at 80% ventilatory threshold for 30 min, 5 days/week) for 3 months in elderly women. In addition, we assessed the plasma concentration of cyclic guanosine monophosphate (cGMP), a second messenger of NO, in the same samples. The individual ventilatory threshold increased significantly after the 3-month exercise training. The blood pressure at rest significantly decreased after exercise training. These results suggest that the 3-month exercise training in the older women produced favorable physiological effects. The plasma concentration of NOx significantly increased by the exercise training, and the plasma concentration of cGMP also increased by the exercise training. The present study suggests that even a mild regular aerobic-endurance exercise increases NO production in previously sedentary older humans, which may have beneficial effects (i.e., antihypertensive and antiatherosclerotic effects by endogenous NO) on the cardiovascular system. (Hypertens Res 2004; 27: 947-953)
We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly. (Hypertens Res 2004; 27: 955-961)
This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n =10), losartan 12.5 mg (n =10), and both (n =11) on mild-to-moderate proteinuria 0.76±0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p =0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy. (Hypertens Res 2004; 27: 963-970)
Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticoid receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (1 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9±49.2 mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0±4.0 mg/day, p =0.0046) and the cilazapril-treated group (71.8±26.0 mg/day, p =0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4±4.5 mg/day, p =0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0±18.4 vs. 80.3±18.5 in the untreated group, p =0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease. (Hypertens Res 2004; 27: 971-978)
To examine the role of serine proteases in the control of aldosterone (Ald) secretion, we studied the effects of nafamostat mesilate (Naf), a serine protease inhibitor, on in vivo Ald secretion and Ald content in the rat adrenal gland. Either Naf (2 mg/kg/h; n =10) or saline (2 ml/h; n =10) was administered intravenously for 30 min to anesthetized Wistar rats whose left adrenal vein was cannulated selectively via the inferior vena cava. Naf caused a significant decrease in Ald secretion rate compared to saline (1.99±0.32 vs. 3.42±0.56 ng/min, p <0.001), while adrenal blood flow, mean arterial pressure and plasma renin activity in the adrenal venous blood did not differ between the two groups. In a separate trial, adrenal Ald content, adrenal renin content, plasma adrenocorticotropic hormone (ACTH) and plasma potassium did not differ between rats treated with Naf (n =7) and those administered saline (n =7). These data suggested that Naf-inhibitable serine proteases may participate in the control of Ald secretion through mechanism(s) other than hemodynamic changes, adrenal renin, ACTH, and/or plasma potassium. (Hypertens Res 2004; 27: 979-984)
We experienced two aged patients with atherosclerotic renovascular stenosis associated with hypertension and ischemic nephropathy. Both patients exhibited sudden rise in blood pressure (BP) and progressive aggravation of renal dysfunction. In these patients, the use of contrast medium to screen for renal artery stenosis (RAS) ran the risk of further deterioration of renal function. We therefore used magnetic resonance angiography (MRA), which is less conducive to renal damage, to screen for RAS. One-sided RAS was treated by percutaneous transluminal angioplasty of the renal artery (PTRA) and stenting. As a result, BP decreased in both patients. Serum creatinine (Cr) decreased slightly in one patient, whereas, in the other, serum Cr increased transiently and then decreased and stabilized to pre-treatment levels. Thus, although it is unclear whether the combination of PTRA and stenting is among the best treatments for patients with RAS and moderate-to-severe renal dysfunction, PTRA and stenting are clearly of benefit in selected patients. In addition, recent progress in characterizing the pathophysiology of ischemic nephropathy associated with renovascular hypertension has created interest in the therapeutic potential of angiotensin II receptor antagonists, sympatholytic agents, and antioxidants. Therefore, we discuss the therapeutic utility of PTRA and stenting and the above-mentioned medications in patients with RAS and renal dysfunction. (Hypertens Res 2004; 27: 985-992)
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Edited and published by : The Japanese Society of Hypertension Produced and listed by : TSUCHIYAMA PRINTING CO., LTD. (2002, Vol. 25. No. 1 - 2004, Vol. 27. No. 12) TO-ON MUSIC PUBLISHING CO.,LTD(2005, Vol. 28. No. 1-)