Hypertension Research
Online ISSN : 1348-4214
Print ISSN : 0916-9636
ISSN-L : 0916-9636
Volume 26 , Issue 1
January
Showing 1-13 articles out of 13 articles from the selected issue
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Original Articles
Clinical studies
  • Mutsuhiro NAKAO, Eiji YANO, Shinobu NOMURA, Tomifusa KUBOKI
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 1 Pages 37-46
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    To examine the blood pressure-lowering effects of biofeedback treatment in patients with essential hypertension, a meta-analysis was conducted on studies published between 1966 and 2001. A total of 22 randomized controlled studies with 905 essential hypertensive patients were selected for review. Compared with clinical visits or self-monitoring of blood pressure (non-intervention controls), biofeedback intervention resulted in systolic and diastolic blood pressure reductions that were greater by 7.3 mmHg (for systole; 95% confidence interval: 2.6 to 12.0) and 5.8 mmHg (for diastole; 95% confidence interval: 2.9 to 8.6). Compared with sham or non-specific behavioral intervention controls, the net reductions in systolic and diastolic blood pressures by biofeedback intervention were 3.9 (95% confidence interval: -0.3 to 8.2) and 3.5 (-0.1 to 7.0) mmHg, respectively. The results of multiple regression analysis also indicated that biofeedback intervention decreased systolic and diastolic blood pressures more than non-intervention controls (p <0.001), but not more than sham or non-specific behavioral intervention controls (p >0.05), when controlling for the effects of initial blood pressures. When biofeedback intervention types were classified into two types, simple biofeedback and relaxation-assisted biofeedback, only the relaxation-assisted biofeedback significantly decreased both systolic and diastolic blood pressures (p <0.05) compared with those in sham or non-specific behavioral intervention controls. The results suggested that biofeedback was more effective in reducing blood pressure in patients with essential hypertension than no intervention. However, the treatment was only found to be superior to sham or non-specific behavioral intervention when combined with other relaxation techniques. Further studies will be needed to determine whether biofeedback itself has an antihypertensive effect beyond the general relaxation response. (Hypertens Res 2003; 26: 37-46)
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  • Mitsunobu MATSUBARA, Hirohito METOKI, Tomohiro KATSUYA, Masahiro KIKUY ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 1 Pages 47-52
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    The angiotensinogen (AGT) gene polymorphism M235T (a methionine to threonine amino acid substitution) has been investigated in association with essential hypertension (EHT) based on conventional measurement of blood pressure (BP); however, the results have been inconsistent. Recently, we have been conducting lines of genetic analysis on a general population of Ohasama Town in Iwate Prefecture, Japan, who measured their BP at home (Ohasama genetic analysis and home BP project). We here assessed the association between AGT M235T polymorphism and hypertension within the same population (1, 245 subjects aged 40 years and over). AGT M235T polymorphism was determined by genotyping the AGT T+31C polymorphism, which has complete disequilibrium with the AGT M235T polymorphism. We defined subjects as hypertensive if they were being treated with antihypertensive medication and/or had home BP values of more than 135 mmHg in systole and/or 85 mmHg in diastole. The genotype frequencies were similar to those in previous Japanese studies. There was no significant difference among the genotypes in home BP values (p =0.63/0.74 for systolic/diastolic blood pressure) or in prevalence of hypertension (MM: 44.7%; MT: 42.3%; TT: 39.6%; p =0.61). No difference was noted in the frequency of familial history of hypertension. Pulse pressure, however, was significantly different among the genotypes (p =0.049), and this association was prominent in the older (age≥60) population (p =0.0018), but not noted in the younger population (60>age≥40). In conclusion, the present analysis confirmed the lack of a significant effect of AGT M235T polymorphism on blood pressure level, but the difference in pulse pressure in the older population suggests that further investigations of this polymorphism should be made in the Japanese population. (Hypertens Res 2003; 26: 47-52)
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  • Hiroyuki SUMINO, Shuichi ICHIKAWA, Yoshio OHYAMA, Tetsuya NAKAMURA, Ts ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 1 Pages 53-58
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    An insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene determines serum ACE levels. The D allele is associated with increased ACE activity and is linked to cardiovascular disease. Hormone replacement therapy (HRT) in postmenopausal women (PMW) decreases serum ACE activity and concomitantly increases plasma bradykinin. We investigated the effect of HRT on these parameters in PMW according to ACE-genotype. We assessed 68 PMW during 12-month oral HRT (0.625 mg conjugated estrogen +2.5 mg medroxyprogesterone acetate). ACE genotype was determined at baseline, and serum ACE activity and plasma bradykinin were measured at baseline and after 3-, 6-, and 12-month HRT. We divided the PMW into three groups according to ACE genotype: groups I/I (n =26), I/D (n =33), and D/D (n =9). HRT resulted in a significant reduction in the genotype-associated increase in ACE activity in the ACE I/D and D/D groups after 6-month (p <0.001 and p <0.05, respectively) and 12-month HRT (p <0.001 and p <0.01, respectively), but not in the I/I group. While the reduction of ACE activity was expected to increase bradykinin in the ACE I/D and D/D groups, HRT significantly increased the bradykinin levels not only in these two groups but also in the ACE I/I group at both 6 months (p <0.01, p <0.05, and p <0.001, respectively) and 12 months after the start of HRT (p <0.01, p <0.01, and p <0.01, respectively). These results suggest that the increased plasma bradykinin of PMW by HRT might not be induced solely by the reduction in serum ACE activity. (Hypertens Res 2003; 26: 53-58)
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  • Satoko TONARI, Hikaru NISHIMURA, Kiyo FUKUNISHI, Tatsuhiko MORI, Yasus ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 1 Pages 59-65
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    Forearm hyperemia, carotid intima-media thickness (IMT), and ankle-brachial pressure index (ABI) are subclinical markers associated with coronary artery disease (CAD). However, it is not known which marker is most highly correlated with CAD. We therefore compared these three parameters in the same patients under 65 years of age. In 40 males with documented CAD (mean age, 53 years), we measured forearm hyperemia by plethysmography, carotid IMT by B-mode ultrasound, and ABI by Doppler ultrasonography. Microalbuminuria, serum lipids, glucose and C-reactive protein (CRP) were also measured. Thirteen normal males served as controls (mean age, 49 years). Compared with normal subjects, CAD patients had lower hyperemia (42 vs. 92%; p <0.001) and greater carotid IMT (0.81 vs. 0.67 mm; p <0.01), but ABI was similar. The sensitivity of forearm hyperemia (72%) was higher than that of carotid IMT (22%) or ABI (3%) (abnormal criteria: forearm hyperemia <60%, carotid IMT ≥1.0 mm, and ABI <0.9). The patients had higher serum low-density lipoprotein (LDL) cholesterol, glucose and CRP, and lower high-density lipoprotein (HDL) cholesterol than the controls. Albuminuria was present in 49% of patients. Subclinical markers were further analyzed by age (35-54 vs. 55-64 years). The sensitivity of carotid IMT was lower in the younger patients (4% vs. 33%), while that of forearm hyperemia (69% vs. 75%) and albuminuria (47% vs. 52%) did not change with age. While carotid ultrasound was useful in older patients (≥ 55 years), forearm hyperemia and microalbuminuria were sensitive markers irrespective of age. ABI was not useful in the Japanese men with CAD under age 65. (Hypertens Res 2003; 26: 59-65)
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Experimental studies
  • Atsuko NOSE, Yasukiyo MORI, Yoko UCHIYAMA-TANAKA, Noriko KISHIMOTO, Ka ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 67-73
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    In the development of diabetic nephropathy, angiotensin (Ang) II is thought to exert numerous actions on the glomerulus, and especially on the mesangium. However, the role(s) played by Ang II in the glucose metabolism per se in mesangial cells remains unclear. Ang II, at least via its type 1 receptor (AT1-R)-mediated effect, phosphorylates extracellular signal regulated kinase (ERK) by transactivation of epidermal growth factor receptors (EGF-Rs) via the Ca2+ or protein kinase C (PKC) pathways. Our objective in the present study was to assess the effect of Ang II on glucose transporter 1 (GLUT1) gene expression and to clarify the involvement of EGF-R in Ang II-mediated GLUT1 mRNA expression in glomerular mesangial cells. The results showed that Ang II upregulated GLUT1 mRNA accumulation in a time- and dose-dependent manner (peaking at 12 h; ~3.8-fold vs. control), and this upregulation was completely inhibited by the PKC inhibitor calphostin-C. The Ang II-induced GLUT1 expression was significantly inhibited by the EGF-R inhibitor AG1478 (~80% inhibition), by inactivation of ERK by PD98059, and by pretreatment with heparin and the metalloproteinase (MMP) inhibitor batimastat. On the other hand, phorbol ester markedly upregulated GLUT1 mRNA (~8.6-fold). Batimostat and AG1478 significantly reduced the phorbol ester-induced GLUT1 mRNA expression (~72 and ~69% inhibition, respectively). In conclusion, PKC-mediated heparin-binding (HB)-EGF/EGF transactivation followed by ERK activation plays a predominant role in the induction of GLUT1 expression by Ang II. (Hypertens Res 2003; 26: 67-73)
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  • J. LEE Soon, Jun LIU, Nianning QI, A. GUARNERA Ross, Si Y. LEE, T. CIC ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 75-87
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    Candidate gene(s) for multiple blood pressure (BP) quantitative trait loci (QTL) were sought by analysis of differential gene expression patterns in the kidneys of a panel of eight congenic strains, each of which carries a different low-BP QTL allele with a genetic composition that is otherwise similar to that of the hypertensive Dahl salt-sensitive (S) rat strain. First, genes differentially expressed in the kidneys of one-month-old Dahl S and salt-resistant (R) rats were identified. Then, Northern filter hybridization was used to examine the expression patterns of these genes in a panel of congenic strains. Finally, their chromosomal location was determined by radiation hybrid (RH) mapping. Seven out of 37 differentially expressed genes were mapped to congenic regions carrying BP QTLs, but only one of these genes, L-2 hydroxy acid oxidase (Hao2), showed the congenic strain-specific pattern of differential kidney gene expression predicted by its chromosomal location. This data suggests that Hao2 should be examined as a candidate gene for the rat chromosome 2 (RNO2) BP QTL. (Hypertens Res 2003; 26: 75-87)
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  • Hiroaki MUKAWA, Yukio TOKI, Yutaka MIYAZAKI, Hideo MATSUI, Kenji OKUMU ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 89-95
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    We investigated the effects of angiotensin II type 2 (AT2) receptor blockade on the antihypertrophic effects of type 1 receptor (AT1) blockade in pressure-overload cardiac hypertrophy in adult rats. Cardiac hypertrophy was induced by banding the abdominal aorta above the renal arteries. The rats were treated with either an AT1 receptor antagonist TCV-116 (TCV, 10 mg/kg/day), an AT2 receptor antagonist PD123319 (PD, 20 mg/kg/day), or both for 4 weeks after the aortic banding. We measured systolic and diastolic blood pressure (BP), body weight (BW), left ventricular weight (LVW), and serum and cardiac angiotensin converting enzyme (ACE) activities. Aortic banding increased BP and LVW/BW, and TCV reversed both these increases. PD affected neither BP nor LVW/BW. TCV+PD reversed the increase in BP but not LVW/BW. Thus, PD was considered to counteract the antihypertrophic effect of TCV without affecting BP. All three treatments reduced cardiac ACE activity without affecting serum ACE activity. Our data demonstrated that AT2 receptor blockade negates the antihypertrophic effects of AT1 receptor blockade in an adult rat model of pressure-overload cardiac hypertrophy. AT2 receptors may mediate the signaling pathways involved in growth inhibition, which could counteract mediation of the cellular growth signaling pathways by AT1 receptors. (Hypertens Res 2003; 26: 89-95)
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  • Masahisa ASANO, Yukiko NOMURA
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 97-106
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    Since Y-27632, a specific inhibitor of Rho kinase, decreases the blood pressure in spontaneously hypertensive rats (SHR), it is suggested that Rho kinase is involved in the pathophysiology of hypertension. However, the effects of Y-27632 on isolated resistance arteries have never been determined. This study aimed to examine the possible role of the Rho/Rho kinase pathway during arterial contraction in isolated resistance arteries from SHR. The profile of arterial relaxant effects of Y-27632 was compared in endothelium-denuded strips of small and large mesenteric arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The addition of 10-6 mol/l norepinephrine (NE) to the strips of small arteries caused an initial peak followed by a tonic contraction in both strains. There was no difference between the two strains in either the initial peak or the tonic contraction. The addition of Y-27632 (0.3-3μmol/l) to the tonic contraction of these strips caused a concentration-dependent relaxation in both strains. The relaxation was greater in SHR than in WKY. Similar results were observed in strips of large arteries. The relaxant effects of Y-27632 were greater in the large artery than in the small artery. Y-27632 also induced a concentration-dependent relaxation in strips precontracted with 65.9 mmol/l K+ depolarization. In both arteries, this relaxation was greater in SHR. The relaxant effects of Y-27632 were greater in the K+-contracted strips than in the NE-contracted strips. We conclude that Y-27632 shows the greater relaxant effects on the SHR arteries, and the effects are more evident in the large artery and in the K+-contracted strips. (Hypertens Res 2003; 26: 97-106)
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  • Hitoshi KAWABATA, Kinji ISHIKAWA
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 107-110
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    We investigated the effects of metformin on myocardial metabolism during ischemia by 31P-nuclear magnetic resonance (NMR) in isolated rabbit hearts. Metformin was administered 60 min prior to induction of global ischemia, or in combination with a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), at 5 min or 60 min prior to the ischemia. Normothermic global ischemia was then carried out for 45 min. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: a control (C) group; an M group receiving metformin treatment alone; an M+L (5) group receiving metformin treatment with L-NAME at 5 min before ischemia; and an M+L (60) group receiving metformin treatment with L-NAME at 60 min before ischemia. During ischemia, the decrease in adenosine triphosphate (ATP) was significantly inhibited in the M group in comparison with the C group (p <0.01). However, this preservation of ATP in the M group was inhibited in the M+L (5) group during ischemia. In contrast, in the M+L (60) group, this preservation of ATP in the M group was not inhibited during, but not at the end of, ischemia. These results suggest that metformin has a significant beneficial effect for improving the myocardial energy metabolism during myocardial ischemia. This cardioprotection may be more dependent on nitric oxide synthase during ischemia than during pre-ischemia. (Hypertens Res 2003; 26: 107-110)
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  • Yoshio FUJIOKA, Miho MASAI, Sayaka TSUBOI, Takahiro OKUMURA, Shinji MO ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 111-116
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    Activation of the Na+/H+ exchanger (NHE) is known to be related to elevated blood pressure in hyperinsulinemia. We previously demonstrated that a fructose-enriched diet induced hyperinsulinemia and hypertriglyceridemia, elevated NHE activity, increased intracellular calcium concentrations ([Ca2+]i), and increased blood pressure in borderline hypertensive rats (BHR). This study examines whether pharmacologically reducing plasma triglyceride or insulin concentrations lowers blood pressure and reduces NHE activity in fructose-fed BHR. Eicosapentaenoic acid (EPA), bezafibrate (BEZ), and troglitazone (TRO) were administered to treat hypertriglyceridemia and/or hyperinsulinemia. Rats were fed a 60% fructose diet or a control diet for 4 weeks, followed by a diet with either vehicle, EPA, BEZ, or TRO for 4 weeks. Intracellular pH (pHi) was measured in platelets by fluorescent dye. Platelet NHE activity was evaluated by the recovery of pHi following addition of sodium propionate (Vmax). [Ca2+]i in platelets were measured fluorometrically. In fructose-fed rats, EPA prevented further increase in blood pressure, and reduced triglyceride concentration and [Ca2+]i without affecting Vmax or plasma insulin concentrations. BEZ reduced triglyceride concentrations without affecting blood pressure, Vmax, [Ca2+]i, or insulin concentrations. TRO prevented an increase in blood pressure, and reduced Vmax, [Ca2+]i, and insulin, but not triglycerides. Plasma insulin and Vmax were positively correlated. In conclusion, improvement of hyperinsulinemia can decrease NHE activity and blood pressure in fructose-fed BHR. (Hypertens Res 2003; 26: 111-116)
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  • Tomoko UENO, Shinya KANAME, Kenmei TAKAICHI, Miki NAGASE, Akihiro TOJO ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 1 Pages 117-122
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    LOX-1 is a novel receptor for oxidized low-density lipoprotein (LDL) isolated from vascular endothelial cells and has been suggested to be involved in the formation of atherosclerotic and hypertensive vascular lesions. We previously reported that salt loading caused glomerulosclerosis and upregulation of LOX-1 in the kidney of Dahl salt-sensitive hypertensive rats. In the present study, we investigated LOX-1 expression in the remnant kidney, an established rat model for chronic renal failure. Six weeks after 5/6 nephrectomy, the rats showed elevated blood pressure, impaired renal function and increased renal expression of type I collagen. The LOX-1 gene expression in the remnant kidney was markedly increased compared with that in control rats, and immunohistochemical analysis showed that LOX-1 was widely expressed in the interstitial cells, whereas there was almost no staining in the glomeruli or tubules. Moreover, reduction of blood pressure by the angiotensin II type 1 (AT1) receptor antagonist candesartan significantly suppressed the renal LOX-1 expression, and this suppression was accompanied by amelioration of renal injury. These results suggest that enhanced renal expression of LOX-1 might play some roles in the progression of chronic renal failure in rats. (Hypertens Res 2003; 26: 117-122)
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Case Report
  • Fumihiko TAKAHASHI, Naoyuki HASEBE, Junko CHINDA, Motoi OKADA, Toshiha ...
    Type: Case Report
    2003 Volume 26 Issue 1 Pages 123-127
    Published: 2003
    Released: August 31, 2003
    JOURNALS FREE ACCESS
    A sixty eight-year-old man was referred to our hospital for evaluation of hypertension and hypokalemia. His chief complaints were fatigability and weakness of the lower extremities. Atrophy of the right kidney was noted on computed tomography. The laboratory findings demonstrated massive proteinuria, markedly elevated plasma renin activity, hypokalemia, and renal insufficiency. Angiography showed total occlusion of the right renal artery. The patient was diagnosed as having nephrotic syndrome associated with renovascular hypertension. Treatment with candesartan, an angiotensin-II-receptor blocker (ARB), controlled both hypertension and proteinuria satisfactorily without worsening of his renal function. This is the first report on the effect of ARB on nephrotic syndrome associated with renovascular hypertension. Based on the results, ARB can be considered a promising agent for the treatment of patients with renovascular hypertension with massive proteinuria and renal insufficiency. (Hypertens Res 2003; 26: 123-127)
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