Hypertension Research
Online ISSN : 1348-4214
Print ISSN : 0916-9636
ISSN-L : 0916-9636
Volume 26 , Issue 4
April
Showing 1-10 articles out of 10 articles from the selected issue
Original Articles
Clinical studies
  • Mayumi MINAMI, Keiichiro ATARASHI, Akihiro ISHIYAMA, Yasunobu HIRATA, ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 4 Pages 273-280
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    We previously demonstrated that normotensive patients with hypercholesterolemia showed excessive blood pressure (BP) responses to stress tests. In this study, we examined the effects of cholesterol-lowering therapy on BP in order to confirm that hypercholesterolemia plays a role in the regulation of BP. Fifteen patients with hypercholesterolemia and 24 normal cholesterolemic controls performed mental arithmetic stress (AS) and hand grip (HG) tests. BP was measured during the tests. Serum lipids and lipid peroxides were measured before the AS. Platelet intracellular free calcium concentration ([Ca2+])i with and without low density lipoprotein (LDL) stimulation, plasma cGMP and NOx were determined immediately before AS and at the end of each test. In hypercholesterolemic patients, the tests were repeated at the end of a 12-week treatment with 10 mg/day of pravastatin, a hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. In hypercholesterolemic patients, BP responses to both tests were greater than those of the controls. Basal and LDL-stimulated platelet [Ca2+]i were higher, and the ratio of plasma cGMP to NOx was lower. Serum total cholesterol, LDL cholesterol and lipid peroxides were significantly decreased in association with the pravastatin treatment. Systolic BP to AS and systolic BP/diastolic BP to HG were decreased (p <0.01, p <0.01/p <0.02, respectively). Platelet [Ca2+]i with LDL stimulation was decreased (p <0.01). Plasma cGMP was increased (p <0.05), whereas NOx was decreased (p <0.05); therefore, the ratio of cGMP to NOx was increased (p <0.05). In conclusion, excessive blood pressure responses to stress tests were improved after cholesterol-lowering therapy. This finding suggests that hypercholesterolemia itself is involved in the regulation of BP. (Hypertens Res 2003; 26:273-280)
    Download PDF (52K)
  • Masahiro NISHINA, Toru KIKUCHI, Hisashi YAMAZAKI, Kazuhiro KAMEDA, Mak ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 4 Pages 281-288
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    The aim of this study was to clarify the relation among systolic blood pressure (SBP), serum insulin, leptin, visceral fat accumulation and family history of hypertension, and to elucidate the pathophysiologic mechanism of blood pressure elevation in obese children. This study examined 109 obese children with a family history of hypertension (OF: 77 boys and 32 girls), and 83 obese children without such a history (ON: 60 boys and 23 girls). Body height and weight, and percent of body fat were measured and the percent of relative weight was calculated. Both boys and girls, the two groups were matched with respect to age, height, and weight. SBP was measured in the seated position using an automated recorder. Abdominal fat thickness (maximum preperitoneal fat thickness: Pmax; minimum subcutaneous fat thickness: Smin) were measured using ultrasonography. The fasting serum levels of insulin and leptin were measured by radioimmunoassay. All subjects were simply obese, without diabetic states. In both OF and ON, SBP was associated with insulin levels, leptin levels, and Pmax by simple regression analysis, and with insulin levels by stepwise regression analysis. Insulin levels were associated with leptin levels and Pmax by simple regression analysis, and with leptin levels by stepwise regression analysis. These findings indicated that SBP was associated with hyperinsulinemia, hyperleptinemia and visceral accumulation regardless of a family history of hypertension in obese children, as well as later in adult obesity. For primary prevention of hypertension, these results support the importance of implementation of a strategy to prevent obesity, especially visceral obesity. An effective strategy for preventing childhood obesity will contribute to a future decrement in cases of metabolic syndrome, including adulthood hypertension. (Hypertens Res 2003; 26: 281-288)
    Download PDF (74K)
  • Kunitoshi ISEKI, Chiho ISEKI, Kazue ITOH, Miho SANEFUJI, Keiko UEZONO, ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 4 Pages 289-294
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    We examined the relation between protein intake and blood pressure in a screened cohort in Okinawa, Japan. A total of 1, 299 screened subjects, 885 men and 414 women, were examined at the Okinawa General Health Maintenance Association. Daily intake of sodium (Na) and potassium (K) was estimated from Na, K, and creatinine excretion by the method of Kawasaki et al., and daily protein intake was estimated by the method of Maroni et al. as the estimated daily urinary excretion of urea nitrogen. Mean (SD) daily protein intake was 71.8 (18.6) g in men and 54.0 (13.5) g in women, and the mean (SD) daily protein intake per unit kg body weight was 1.1 (0.2) g/kg in men and 1.0 (0.2) g/kg in women. In men, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in those with lower protein intake (LP; <1.0 g/kg/day) than in those with higher protein intake (HP; ≥ 1.0 g/kg/day) (p <0.05 for DBP). In women, both SBP and DBP were higher in those with LP than in those with HP, but these differences were not statistically significant. However, urinary excretion of both Na and K was lower in those with LP than in those with HP, respectively, both in men and women (p <0.0001). In summary, estimated daily protein intake was about 1.1 g/kg in men and 1.0 g/kg in women. Despite the higher urinary excretion of Na, both SBP and DBP tended to be lower in those with higher daily protein intake, particularly in men. (Hypertens Res 2003; 26: 289-294)
    Download PDF (365K)
  • Hirofumi TOMIYAMA, Toshio KUSHIRO, Ryo OKAZAKI, Hideo YOSHIDA, Nobutak ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 4 Pages 295-300
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    The effect of oxidative stress on endothelial function, platelet function, and fibrinolysis in hypertension with or without glucose intolerance was examined. The endothelium, platelets and fibrinolysis play important roles in the progression of atherosclerosis and interact with each other. We have previously demonstrated that glucose intolerance impairs endothelial function in hypertension, but its precise mechanisms have not been clarified. Hypertensive patients were divided by the results of 75-g oral glucose tolerance test into a normal glucose metabolism group (n =65) and a glucose intolerance group (n =47). The plasma level of thiobarbituric acid-reactive substances (TBARS) was assessed as a marker of oxidative stress. Endothelial function was assessed by flow-mediated dilatation (FMD), platelet function by the concentration of ADP dose inducing half-maximal aggregation (EC50), and fibrinolytic parameters by radioimmunoassay. These functions were assessed before and after acute administration of vitamin C. FMD was reduced while TBARS and fibrinolytic parameters were higher in patients with glucose intolerance than in those with a normal glucose metabolism. Vitamin C increased FMD and reduced fibrinolytic parameters significantly in the glucose intolerance group, but not in the group with normal glucose metabolism. On the other hand, the EC50 was similar in both groups. In conclusion, glucose intolerance aggravates oxidative stress, thereby contributing to the impairment of endothelial function in patients with hypertension. These abnormalities affect fibrinolysis but not platelet function. (Hypertens Res 2003; 26: 295-300)
    Download PDF (36K)
  • Chihiro TANAKA, Kei KAMIDE, Shin TAKIUCHI, Yoshikazu MIWA, Masayoshi Y ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 4 Pages 301-306
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    Insertion/deletion (I/D) polymorphisms in intron 16 of the angiotensin converting enzyme gene (ACE) are associated with the plasma angiotensin converting enzyme (ACE) levels, and individuals with the DD allele have been reported to be more susceptible to cardiovascular disease than those without. The conventional genotyping method for the screening of I/D polymorphisms, which involves polymerase chain reaction (PCR)-gel electrophoresis, is laborious and time-consuming. In this study, we assessed the use of TaqMan-PCR genotyping for the screening of I/D polymorphisms as a replacement for the conventional method. We genotyped seven single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with the I/D polymorphisms, and calculated the LD coefficients of the I/D polymorphisms. We found that three polymorphisms, rs4331, rs4334 and rs4341, exhibited the highest LD coefficients (D′=1.000; r2 =0.967) and that the genotyping of rs4341 by the TaqMan-PCR method yielded the best discrimination among the different genotypes. Genotyping of 511 samples took only 2 h and the amount of DNA required for each test was only 6 ng by the TaqMan-PCR method using rs4341. In the course of this study, we identified a novel additional polymorphism (a deletion of six amino acids) in exon 13, near rs4316. The deletion allele encoded the testicular ACE, but not the plasma ACE. We concluded that genotyping of the rs4341 ACE polymorphism by the TaqMan-PCR method is a fast and convenient alternative method for direct I/D genotyping. We also concluded that testicular ACE may manifest a deletion of six amino acids that may result in deleterious function of this enzyme. (Hypertens Res 2003; 26: 301-306)
    Download PDF (42K)
  • Jong Il KIM, Takeshi TSUJINO, Yoshio FUJIOKA, Komei SAITO, Mitsuhiro Y ...
    Type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 4 Pages 307-313
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140±2.6 to 131.8±2.6 mmHg, mean±SEM), diastolic blood pressure (DBP) (87.8±2.0 to 82.8±2.6 mmHg), fasting plasma triglyceride concentration (225.5±23.5 to 102.9±10.9 mg/dl), fasting plasma insulin concentration (9.6±0.8 to 7.1±0.8 μU/ml), and homeostasis model assessment scores (HOMA-R, 2.4±0.2 to 1.7±0.2), and significantly improved the insulin sensitivity index (56.0±3.0 to 70.7±4.8 mg・l2/mmol・mU・min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r =0.50, p <0.01) and SFA (r =0.39, p <0.05), and negatively correlated with PUFA (r =-0.45, p <0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders. (Hypertens Res 2003; 26: 307-313)
    Download PDF (47K)
Experimental studies
  • Shinji MORIMOTO, Yoshio FUJIOKA, Hiroshi HOSOAI, Takahiro OKUMURA, Mih ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 4 Pages 315-323
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    Triglyceride-rich lipoproteins have been suggested to promote atherosclerosis. Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in the events of cardiovascular pathophysiology. The renin-angiotensin system influences various vascular functions, including PAI-1 production. We examined whether or not chylomicron remnants increased PAI-1 mRNA and protein production in endothelial cells and whether or not an inhibition of the renin-angiotensin system interfered with this effect. Chylomicron remnants were isolated from functionally hepatectomized rats injected with chylomicrons. Human umbilical vein endothelial cell cultures (HUVECs) were incubated with chylomicron remnants with or without an angiotensin-converting enzyme inhibitor (temocaprilat), an angiotensin II receptor type 1 antagonist (RNH-6270), or an angiotensin II receptor type 2 antagonist (PD123319). Chylomicron remnants increased PAI-1 secretion in HUVECs (0.5 μg/ml; 128.3±6.1%, the mean±SEM) as well as angiotensin II (10 nmol/l; 130.7±9.5%) in 18 h, as compared with the controls, as well as stimulated PAI-1 mRNA expression to a maximum level at 4 h. Temocaprilat and RNH-6270, but not PD123319, attenuated all of these effects. Chylomicron remnants enhanced nuclear extract binding to a very low-density lipoprotein response element in the PAI-1 promoter region and activated nuclear factor-κB. Extracellular signal-regulated kinase (ERK 1/2) was phosphorylated in response to chylomicron remnants. These effects were inhibited by temocaprilat or RNH-6270. In conclusion, chylomicron remnants increased protein secretion and mRNA expression of PAI-1 in HUVECs. Inhibition of the renin-angiotensin system reduced this stimulation. (Hypertens Res 2003; 26: 315-323)
    Download PDF (115K)
  • Yoshitaka HIROOKA, Koji SAKAI, Takuya KISHI, Koji ITO, Hiroaki SHIMOKA ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 4 Pages 325-331
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    Previously, we demonstrated that endothelial nitric oxide synthase (eNOS) gene transfer into the nucleus tractus solitarii (NTS) decreased blood pressure, heart rate and sympathetic nerve activity in conscious normotensive Wistar-Kyoto rats (WKY). In order to determine whether overexpression of eNOS in the NTS causes different effects on blood pressure and heart rate between spontaneously hypertensive rats (SHR) and WKY, we transfected adenovirus vectors encoding either eNOS (AdeNOS) or β-galactosidase (Ad β gal) into the NTS of SHR and WKY in vivo. The local expression of eNOS in the NTS was confirmed by Western blot analysis for eNOS protein, and the magnitude of expression did not differ between SHR and WKY. Blood pressure and heart rate were monitored by the use of a radio-telemetry system in a conscious state before and 7 days after the gene transfer. Systolic blood pressure (SBP) and heart rate decreased on day 7 in both AdeNOS-transfected SHR and WKY. However, the magnitude of decreases in SBP of AdeNOS-transfected SHR was greater than that of AdeNOS-transfected WKY (-24.1±2.9 vs. -15.9±2.1 mmHg, p <0.05). Transfection of Ad β gal into the NTS did not alter SBP in either group. A depressor response evoked by microinjection of L-glutamate into the NTS did not differ between the two strains. These results suggest that overexpression of eNOS in the NTS causes a greater depressor response in SHR than in WKY in a conscious state. An abnormality of the L-arginine-NO pathway in the NTS may be related to the hypertensive mechanism(s) of SHR. (Hypertens Res 2003; 26: 325-331)
    Download PDF (50K)
  • Karla MAZANCOVÁ, Ivan MIKŠÍK, Jaroslav KUNE&Scaro ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 4 Pages 333-338
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    To evaluate the role of sexually dimorphic tissue expression of 11β-oxidase activity of 11β-hydroxysteroid dehydrogenase (11βHSD) in gender-associated blood pressure differences, we have studied female and male hypertensive rats of two different strains and their normotensive controls: spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY) and Dahl salt-sensitive (SS/Jr) and salt-resistant rats (SR/Jr). In hypertensive SHR and SS/Jr, but not in normotensive strains WKY and SR/Jr, blood pressure reached a higher level in males than in females. The activity of 11βHSD was higher in the renal cortex, medulla, colon and aorta of males than of females in all investigated strains with the exception of aortic 11βHSD in SHR and WKY rats, both of which had very low 11β-oxidase activity. In contrast to gender-dependent differences, strain differences of 11βHSD were observed in a limited number of tissues only. Renal medullary 11βHSD showed significantly lower activity in WKY than in SHR, whereas no difference was observed in the renal cortex. Similarly, colonic 11βHSD activity was lower in WKY than in SHR. In Dahl rats the strain differences were observed in aortic 11βHSD that had higher activity in SR/Jr than in SS/Jr rats; no difference was observed in the kidney or colon. These data demonstrate the following. 1) Sexual dimorphism of 11βHSD activity exists in the kidney, colon, and aorta. 2) The sexual dimorphism of 11βHSD does not play a role in gender-associated differences in blood pressure. 3) The reduced 11βHSD activity in the aorta of hypertensive SS/Jr compared to SR/Jr rats suggests that this enzyme might play a role in the pathogenesis of salt-sensitive hypertension in Dahl rats. (Hypertens Res 2003; 26: 333-338)
    Download PDF (36K)
  • Goro IMAI, Takeo SATOH, Toshio KUMAI, Mei MURAO, Hiroki TSUCHIDA, Yosh ...
    Type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 4 Pages 339-347
    Published: 2003
    Released: November 06, 2003
    JOURNALS FREE ACCESS
    Although it is known that diabetic nephropathy is accelerated by hypertension, the mechanisms involved in this process are not clear. In this study we aimed to clarify these mechanisms using male Wistar fatty rats (WFR) as a type 2 diabetic model and male Wistar lean rats (WLR) as a control. Each group was fed a normal or high sodium diet from the age of 6 to 14 weeks. We determined the blood pressure and urinary albumin excretion (UAE). At the end of the study, the expressions of mitogen-activated protein kinases (MAPK) and transforming growth factor-β1 (TGF-β1) were examined in the isolated glomeruli by Western blot analysis, and the number of glomerular lesions was determined by conventional histology. High sodium load caused hypertension and a marked increase in UAE in the WFR but not in the WLR. Glomerular volume was increased in the hypertensive WFR. There was no difference among the four groups in the expression of c-Jun-NH2-terminal kinase (JNK). In contrast, the expressions of extracellular signal-regulated kinase 1/2 (ERK1/2) and its upstream regulator, MAPK/ERK kinase 1 (MEK1), were augmented in the hypertensive WFR. Expression of p38 MAPK was increased in the normotensive WFR, and further enhanced in the hypertensive WFR. Moreover, administration of high sodium load to WFR augmented the expression of TGF-β1. In conclusion, systemic hypertension in WFR accelerates the diabetic nephropathy in type 2 diabetes via MEK-ERK and p38 MAPK cascades. TGF-β1 is also involved in this mechanism. (Hypertens Res 2003; 26: 339-347)
    Download PDF (134K)
feedback
Top