Hypertension Research
Online ISSN : 1348-4214
Print ISSN : 0916-9636
ISSN-L : 0916-9636
Volume 26, Issue 2
February
Displaying 1-10 of 10 articles from this issue
Original Articles
Clinical studies
  • Koh ONO, Toshifumi MANNAMI, Shunroku BABA, Naomi YASUI, Toshio OGIHARA ...
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 131-134
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    Angiotensin II type 1 (AT1) receptor mediates the vasoconstriction and growth-promoting effect of angiotensin II in humans. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166; A1166C) may be associated with essential hypertension (HT). However, several conflicting results have also been reported. Therefore, we conducted an association study between A1166C variants of the AT1 receptor gene and hypertension in the Japanese population. We genotyped this variant in 3, 918 subjects (1, 492 hypertensive subjects and 2, 426 normotensive subjects) recruited from the Suita study. In subjects not receiving antihypertensive medication, the influence of the genotype on blood pressure values adjusted for clinical covariates was analyzed. The genotype distribution did not differ between hypertensive and normotensive subjects in either men (frequency of the C allele: 8.1% vs. 7.8%, p =0.74) or women (8.1% vs. 7.7%, p =0.60). There were no significant differences in systolic blood pressure, diastolic blood pressure, or pulse pressure among the three genotypes in either men or women who had not received hypertensive medication. Our data suggest that the A1166C polymorphism of AT1 receptor is unlikely to influence blood pressure status in the Japanese population. (Hypertens Res 2003; 26: 131-134)
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  • Kiyoko NISHIJIMA, Osamu TOCHIKUBO
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 135-140
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    In the past, cross-sectional studies of small groups have not always shown a significant relation between habitual sodium intake and blood pressure (BP). This study examined the relation between 24-h urinary sodium excretion (Salt24, g/day) and BP during sleep in young subjects. The subjects were 132 medical students (93 males, 39 females) aged 21 to 26 years, with no renal disorder. Urine was collected for 24 h, and sodium (Na), chloride (Cl), and creatinine (Cr) excretion were measured. The 24-h urinary Cr excretion (Cr24) was compared with the Cr24 estimated from lean body mass as a guide to ensure accurate collection of 24-h urine. The natural logarithm [ln (Salt24/Cr24)] was taken as an index of sodium intake. On the same day, a portable multi-biomedical recorder (TM2425) was used to measure 24-h systolic BP (SBP) /diastolic BP (DBP). Daytime BP was calculated as the average of waking-time BP, and sleep BP was taken as statistical base BP (minimum BP) during nighttime sleep. No correlation was observed between ln (Salt24/Cr24) and daytime BP. The correlation coefficient with sleep SBP, on the other hand, was 0.34 (p <0.05) in the male group and 0.54 (p <0.01) in the male high-BP group (24-h BP>127/75 mmHg, n =28). No relation of this kind was observed in the female group. In conclusion, despite the small number of subjects, the present cross-sectional study revealed a significant positive correlation between sodium intake and sleep SBP in young men with high BP. (Hypertens Res 2003; 26: 135-140)
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  • Masahiro KIKUYA, Ken SUGIMOTO, Tomohiro KATSUYA, Michiko SUZUKI, Tomom ...
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 141-145
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    We previously investigated the relation between hypertension and each of three major genetic polymorphisms in the renin-angiotensin (AGT)-aldosterone system (R-A-A), AGT M235T, angiotensin convert enzyme (ACE) I/D, and CYP11B2 -344C/T, by means of ambulatory blood pressure (ABP) monitoring in a general Japanese population (the Ohasama Study). A/C1166 gene polymorphism in the 3′ untranslated region of the angiotensin II type 1 receptor (AT1) gene is the final remaining major target in R-A-A to be examined in the Ohasama Study population. In the present study, the AT1 A/C1166 polymorphism was genotyped by the TaqMan polymelase chain reaction (PCR) method or restriction fragment length polymorphism (RFLP) in 802 Japanese subjects aged 40 and over, who were previously genotyped for the AGT M235T, ACE D/I, CYP11B2 -344C/T polymorphisms. The AA genotype, AC genotype, and CC genotype were present in 678 (84.5%), 121 (15.1%), and 3 (0.4%) of subjects, respectively. Since the frequency of the C allele was quite low (0.079), the genotypes were classified according to the presence or absence of the C allele. Although daytime blood pressure (BP) was higher in subjects with the C allele, the difference was not statistically significant after adjusting for age, gender, body mass index, and smoking status. No significant difference was noted in the prevalence of cardiovascular diseases or nocturnal BP decline between the two groups. These results indicated that AT1 A/C1166 polymorphism was not associated with any clinical parameters associated with hypertension or atherosclerosis in the Japanese population. (Hypertens Res 2003; 26: 141-145)
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  • Keiji MATSUDA, Hiroki TERAGAWA, Yukihiro FUKUDA, Keigo NAKAGAWA, Yukih ...
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 147-152
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    Recent studies have shown that leptin causes vasodilation. However, it is unclear whether leptin causes coronary vasodilation in humans. To determine how leptin affects human coronary arteries and whether endothelium-derived nitric oxide (EDNO) is involved in the coronary arterial response to leptin, we infused leptin (0.3, 3 and 30 ng/kg/min) for 2 min into the left coronary ostium before and after an infusion of nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in 11 men with angiographically normal coronary arteries. The diameter of the epicardial coronary arteries was quantitatively measured, and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. The changes in these parameters in response to leptin are expressed as the % change from the baseline values. Leptin caused coronary dilation (0.3 ng/kg/min: 2.0±0.5%; 3 ng/kg/min: 4.9±0.7%; 30 ng/kg/min: 3.8±0.9%) and increased CBF (13.6±3.3%, 36.8±5.6%, and 39.2±7.4%, respectively). After the infusion of L-NMMA, leptin also caused coronary dilation (2.0±0.4%, 4.5±0.7%, and 4.6±0.8%, respectively) and increased CBF (14.6±2.8%, 39.2±5.7%, 40.3±6.2%, respectively). Leptin-induced coronary vasodilation was not affected by the infusion of L-NMMA. These results suggest that leptin dilates coronary arteries in humans. Furthermore, EDNO may not contribute to leptin-induced coronary dilation. (Hypertens Res 2003; 26: 147-152)
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  • Taku INOUE, Mitsuteru MATSUOKA, Kazufumi NAGAHAMA, Chiho ISEKI, Takash ...
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 153-158
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    We evaluated the association between pulse pressure (PP) and cardiovascular risk factors in a screened cohort. Individuals who were receiving medications for hypertension or heart disease, who had no ECG record, or who had a record of arrhythmia were excluded. In total, 8, 508 subjects (5, 299 men and 3, 209 women; age range, 18 to 89 years) were studied. Subjects were divided into four PP classes: PP.1 (PP≤40 mmHg, n =2, 127), PP.2 (40≤ PP≤44 mmHg, n =2, 127), PP.3 (44≤PP≤50 mmHg, n =2, 127) and PP.4 (50 mmHg≤PP, n =2, 127). Multiple regression analysis was used for evaluating the association between PP and cardiovascular risk factor or lifestyle. In men, the regression coefficient was 0.27 for age, 2.50 for diabetes mellitus, 0.33 for uric acid, 0.20 for body mass index, 0.07 for heart rate, -0.83 for current smoking habit and 1.23 for habitual drinking. In women, the regression coefficient was 0.37 for age, 4.09 for diabetes mellitus, 0.42 for body mass index, 0.14 for heart rate, and 0.84 for habitual exercise. In both men and women, PP was significantly increased in association with an increase in the number of risk factors (diabetes mellitus, obesity, current drinking status, heart rate, and hyperuricemia). In conclusion, higher PP was associated with cardiovascular risk factors. These associations were similar in both men and women. (Hypertens Res 2003; 26: 153-158)
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  • Ikuo SAITO, Takao SARUTA
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 159-162
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    Sufficient persistence with therapy is important to achieve the desired benefits of antihypertensive therapy. This study was designed to describe the rates of persistence with antihypertensive therapy for 1 year and to assess the effect of patient education by a periodic newsletter on persistence rates in general practice in Japan. Information on 5, 324 patients who received the newsletter once a month for 1 year (intervention group; 53.9% of those originally registered) and 666 patients who did not receive the newsletter (control group; 94.3% of those originally registered) was obtained from a physician questionnaire (response rate: 54.3%). The rate of persistence with antihypertensive therapy in the intervention group was similar to that in the control group (91.7% vs. 90.7%, respectively). The patient questionnaire (response rate: 28.2%) indicated that most patients consistently read the newsletter and found it useful in understanding the management of hypertension. The results of this 1-year study showed that about 90% of patients persisted with therapy for 1 year. Although most of them evaluated the newsletter favorably, no clear effect of the newsletter on their persistence with therapy was revealed. However, these results do not rule out a possible effect of education on persistence with therapy over the long-term, and thus there is need of a longer-term study employing follow-up questionnaires. (Hypertens Res 2003; 26: 159-162)
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  • Udai NAKAMURA, Masanori IWASE, Sakae NOHARA, Hidetoshi KANAI, Kojiro I ...
    Article type: Original Article
    Subject area: Clinical studies
    2003 Volume 26 Issue 2 Pages 163-167
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    At present, brachial-ankle pulse wave velocity (baPWV) can be measured easily and noninvasively. We studied the correlation between aortic damage estimated by baPWV and that determined by measuring the length of abdominal aortic calcification (AAC) on X-ray films, which parameter has been significantly associated with cardiovascular morbidity and mortality. baPWV was measured using the form PWV/ankle brachial index (ABI) device in 97 patients free of end-stage renal failure or peripheral arterial disease. baPWV correlated significantly with age (r2 =0.625, p <0.0001), was significantly higher in hypertensives than in normotensives (2, 109±67 vs. 1, 623±93 cm/s, p <0.0001), and correlated significantly with systolic blood pressure (r2 =0.64, p <0.0001) and diastolic blood pressure (r2 =0.397, p <0.0001). baPWV was significantly higher in diabetic patients than in nondiabetics (2, 068±73 vs. 1, 813±97 cm/s, p <0.05), but was similar in normolipidemic and hyperlipidemic patients. baPWV did not correlate with body mass index, fasting plasma glucose, total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol or triglyceride levels, but correlated significantly with AAC length (r2 =0.599, p <0.0001). Multiple regression analysis indicated that age, systolic blood pressure and AAC length were independent determinants of baPWV. Our results indicate that baPWV is useful for estimating aortic damage and could be a potentially useful predictor of vascular morbidity and mortality. (Hypertens Res 2003; 26: 163-167)
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Experimental studies
  • Masaya HYAKUKOKU, Katsuhiro HIGASHIURA, Nobuyuki URA, Hideyuki MURAKAM ...
    Article type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 2 Pages 169-176
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    The relation between insulin resistance/hyperinsulinemia and cardiovascular diseases has attracted much attention. Insulin affects not only glucose metabolism, but also protein synthesis and cell growth. Insulin stimulates both the phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways, but the relationship between cardiovascular disease and selective insulin signal pathways is unclear. We investigated the tissue specificity and intracellular signal transduction selectivity of insulin resistance in the vasculature and skeletal muscle of fructose-fed rats (FFR). Sprague-Dawley rats were fed either normal rat chow (control rats) or fructose-rich chow. Normal saline with or without 1, 000 (μg/kg) insulin was injected, and then the thoracic aorta or soleus muscle was removed under anesthetization. Insulin-induced tyrosine phosphorylation of insulin receptor β subunit (IRβ) and insulin receptor substrate-1 (IRS-1) and tyrosine/threonine phosphorylation of p44/42 MAPK (ERK-1/2) were evaluated. There were no significant differences in the degree of phosphorylation of IRβ or ERK-1/2 in the thoracic aorta or in the soleus muscle between FFR and controls. However, tyrosine phosphorylation of IRS-1 in the soleus muscle of FFR was significantly reduced to 80% (p <0.001) of that in controls. The results suggest that PI3-K pathway in skeletal muscle is selectively impaired in FFR, and this impairment may induce hyperinsulinemia, which in turn may stimulate the MAPK pathway and lead to atherosclerosis. Thus PI3-K pathway may be one of the factors underlying the onset of cardiovascular disease in patients with insulin resistance. (Hypertens Res 2003; 26: 169-176)
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  • Tatsuo HASHIMOTO, Minoru KIHARA, Keiko YOKOYAMA, Takayuki FUJITA, Syun ...
    Article type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 2 Pages 177-184
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    In cultured vascular smooth muscle cells (VSMCs), interleukin-1β (IL-1β) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. IL-1β also activates phospholipase A2 (PLA2), and induces lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). The present study investigated whether these metabolites are involved in the regulation of IL-1β-induced NO production and iNOS expression. Pretreatment with ONO-RS-082, the secretory PLA2 (sPLA2) inhibitor, at 1 to 10μmol/l reduced IL-1β-stimulated nitrite production and iNOS expression. Nordihydroguaiaretic acid (NDGA, 1 to 10μmol/l), the LOX inhibitor, also reduced IL-1β (10 ng/ml)-stimulated nitrite production and iNOS expression in a dose-dependent manner. Exogenous 12(S)-hydroxyeicosatetraenoic acids (HETE) enhanced the IL-1β-stimulated nitrite production and iNOS expression. On the other hand, the COX inhibitors, indomethacin and NS-398, had little effect on nitrite production or iNOS expression. These results suggest that LOX products play important roles in the regulation of stimulus-induced NO production in VSMCs. (Hypertens Res 2003; 26: 177-184)
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  • Atsushi NUMABE, Nusrat ARA, Rie HAKAMADA-TAGUCHI, Noriko SUZUKI, Nobuh ...
    Article type: Original Article
    Subject area: Experimental studies
    2003 Volume 26 Issue 2 Pages 185-191
    Published: 2003
    Released on J-STAGE: September 28, 2003
    JOURNAL FREE ACCESS
    Among the consequences of the increasing prolongation of lifespan is a worldwide increase in the number of cases of dementia or impaired cognition. In the present study, to test the hypothesis that mechanisms independent of high blood pressure are involved in maintaining cognitive function, we assessed the effects of long-term dilazep treatment on cognitive dysfunction in normotensive Dahl salt-sensitive (Dahl S) rats fed a low-salt diet, using the standard passive avoidance test. Normotensive Dahl S rats fed a 0.3% NaCl diet were treated for 6 months with low-dose dilazep (2.5μg/ml in drinking water) or high-dose dilazep (12.5μg/ml). Systolic blood pressure was within normotensive range throughout the study and did not differ among the experimental groups. The results of the passive avoidance test revealed that dilazep treatment attenuated the decline of latency time relative to that in the untreated control rats (control latency time, 235 s; low-dilazep group, 389 s; high-dilazep group, 397 s), suggesting that the cognitive function of normotensive Dahl S rats was improved by dilazep treatment. This improvement of cognition was associated with significant increases in the number of neuronal cells in the hippocampal region and with an increase in capillary length in dilazep-treated Dahl rats. In addition, the dilazep treatments significantly attenuated arteriolar injury of glomeruli in the kidney. These data suggest that dilazep treatment, through vascular and non-vascular effects, maintains the brain function in Dahl S rats susceptible to vascular injury and organ dysfunction. (Hypertens Res 2003; 26: 185-191)
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