Hypertension: Ouchi Y

Kojima T, Ouchi Y. · Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo. · Nippon Rinsho. · Pubmed #15948373 No free full text.

Abstract: Our understandings about hypertension has increased as results of epidemiological programs issuing about preventions of cardiovascular disease, which started mostly in the latter half of 20th century and now it is known as the one of the most influencing risk factors of cardiovascular and cerebrovascular disease in the developed countries. We were able to get plenty information about the pathophysiology of hypertension and several randomized controlled trials were committed according to these information. Here we will discuss about the epidemiology of elderly hypertension.

Ogihara T, Hiwada K, Morimoto S, Matsuoka H, Matsumoto M, Takishita S, Shimamoto K, Shimada K, Abe I, Ouchi Y, Tsukiyama H, Katayama S, Imai Y, Suzuki H, Kohara K, Okaishi K, Mikami H. · Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. · Hypertens Res. · Pubmed #12661910 links to  free full text

This publication has no abstract.

Ogihara T, Morimoto S, Okaishi K, Hiwada K, Matsuoka H, Matsumoto M, Takishita S, Shimamoto K, Shimada K, Abe I, Ouchi Y, Tsukiyama K, Katayama S, Imai J, Suzuki H, Kohara K, Mikami H. · Third Department of Internal Medicine, Hiroshima University School of Medicine. · Nippon Ronen Igakkai Zasshi. · Pubmed #12073597 No free full text.

This publication has no abstract.

Ohike Y, Kozaki K, Iijima K, Eto M, Kojima T, Ohga E, Santa T, Imai K, Hashimoto M, Yoshizumi M, Ouchi Y. · Department of Geriatric Medicine, University of Tokyo Graduate School of Medicine, Japan. · Circ J. · Pubmed #15671617 links to  free full text

Abstract: BACKGROUND: Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. METHODS AND RESULTS: In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. CONCLUSION: Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.

Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y. · Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan. · Hypertens Res. · Pubmed #18360020 No free full text.

Abstract: Age-related decline of plasma dehydroepiandrosterone-sulfate (DHEA-S) levels may be associated with the risk of cardiovascular disease in women. We investigated whether plasma DHEA-S levels are related to endothelial function in postmenopausal women with coronary risk factors. One hundred and fifteen postmenopausal women (mean age+/-SD: 57+/-5 years; range: 48-65 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. Plasma hormone levels were determined in the morning after a 14-h fast, and the relationship between hormone levels and FMD was analyzed. DHEA-S was significantly correlated with %FMD (r=0.392, p<0.001), while estradiol, total testosterone and cortisol were not. %FMD in the highest quartile of DHEA-S was 1.8-fold higher than that in the lowest quartile (5.3+/-1.3 vs. 2.9+/-2.0 [means+/-SD], p<0.01). Multiple regression analysis revealed that DHEA-S was related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (beta=0.344, p<0.01), and was itself independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and smoking (beta=0.291, p<0.05). In conclusion, plasma DHEA-S levels were weakly but significantly related to endothelial function in postmenopausal women independent of other coronary risk factors, suggesting a protective effect of DHEA on the endothelium.

Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y. · Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Hypertens Res. · Pubmed #18250551 No free full text.

Abstract: We investigated whether a low plasma testosterone level is related to endothelial dysfunction in men with coronary risk factors. One hundred and eighty-seven consecutive male outpatients (mean age+/-SD: 47+/-15 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. The relationship between plasma hormones and FMD was analyzed. Total and free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were significantly correlated with %FMD (r=0.261, 0.354 and 0.295, respectively; p<0.001), while estradiol and cortisol were not. %FMD in the highest quartile of free testosterone was 1.7-fold higher than that in the lowest quartile. Multiple regression analysis revealed that total and free testosterone were related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (beta=0.198 and 0.247, respectively; p<0.01), and were independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, smoking and nitroglycerin-induced dilation (beta=0.196 and 0.227, respectively; p<0.01). DHEA-S was not significantly related to %FMD in multivariate analysis. In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium.

Yamamoto H, Teramoto S, Yamaguchi Y, Hanaoka Y, Ishii M, Hibi S, Ouchi Y. · Department of Geriatric Medicine, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. · Sleep Med. · Pubmed #17512795 No free full text.

Abstract: BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients compared to an age-matched control group. We further hypothesized that oxygen administration treatment may decrease OSAS-induced hypoxic stress and ADM levels. METHODS: We examined short-term and long-term oxygen administration effects on circulating ADM in 48 OSAS patients. RESULTS: The circulating levels of ADM in untreated OSAS patients were significantly greater than those in the controls. We did not observe a significant effect in 2 weeks of oxygen administration on the circulating ADM in the patients, but we observed a significant effect in long-term oxygen administration for more than 3 months on plasma ADM levels. Long-term oxygen therapy decreased both the magnitude of arterial oxygen desaturation and plasma ADM levels in patients but did not decrease blood pressure. CONCLUSIONS: These observations suggest that long-term oxygen therapy could reduce OSAS-induced nocturnal hypoxemia and plasma ADM levels in patients with OSAS.

Eto M, Toba K, Akishita M, Kozaki K, Watanabe T, Kim S, Hashimoto M, Ako J, Iijima K, Sudoh N, Yoshizumi M, Ouchi Y. · Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. · Hypertens Res. · Pubmed #15969248 No free full text.

Abstract: Blood pressure variability is one of the characteristic features of hypertension in the elderly. However, its clinical significance remains to be determined. We therefore examined the impact of blood pressure variability on the development of cardiovascular events in elderly hypertensive patients. A total of 106 consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/- 8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure monitoring, were followed up (median, 34 months; range, 3-60 months). During the follow-up period, 39 cardiovascular events were observed, including 14 cases of cerebral infarction and 7 cases of acute myocardial infarction. The coefficient of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an index of blood pressure variability. The patients showed a mean CV value of 10.6%, and were divided into two groups according to this mean value as a cut-off point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline clinical characteristics were similar in the two groups, Kaplan-Meier plots for event-free survival revealed that the rate of cardiovascular events was significantly higher in high CV group than in low CV group (p < 0.05). Cox's proportional hazards analysis showed that increased blood pressure variability (a high CV value of 24-h SBP) was an independent predictive variable for cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h SBP and daytime SBP also had positive correlations with the onset of cardiovascular events. These results suggest that increased blood pressure variability may be an independent risk factor for cardiovascular events in elderly hypertensive patients.

Eto M, Toba K, Akishita M, Kozaki K, Watanabe T, Kim S, Hashimoto M, Sudoh N, Yoshizumi M, Ouchi Y. · Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. · Hypertens Res. · Pubmed #14717342 links to  free full text

Abstract: Increased short-term blood pressure variability is known to be associated with hypertensive target organ damage. Sinoaortic denervation (SAD) induces a marked increase in blood pressure lability without affecting the average blood pressure level. The aim of this study was to investigate the effects of blood pressure lability on endothelial vasomotor function and neointimal formation after balloon injury in SAD rats. Direct longterm measurement of mean arterial pressure showed no significant difference in the average of mean arterial pressure between the SAD group and sham-operated control group. In contrast, the standard deviation of mean arterial pressure, as an index of blood pressure lability, was 3-fold greater in SAD rats. To study endothelial function, isometric tension of aortic rings was measured 4 weeks after SAD or sham operation. Endothelium-dependent vasorelaxation induced by acetylcholine was significantly reduced in the SAD group (20% reduction at maximum relaxation). Endothelium-independent vasorelaxation induced by sodium nitroprusside was similar in each group. Acetylcholine-induced NO release from aortic rings was significantly reduced in the SAD group. Next, we examined neointimal formation in carotid arteries in SAD and sham-operated rats at 2 weeks after balloon injury. The neointimal-to-medial area ratio in the SAD group was 50% higher than that in the sham-operated group. The percentage of proliferating cell nuclear antigen-positive cells in the intima was significantly higher in the SAD group. These findings suggest that increased blood pressure lability, independently of average blood pressure level, impairs endothelial function by inhibiting NO production, enhances neointimal formation after balloon injury, and may thereby contribute to atherogenesis.

Teramoto S, Kume H, Matsuse T, Ishii T, Miyashita A, Akishita M, Toba K, Ouchi Y. · Department of Geriatric Medicine, Tokyo University Hospital, 7-3-1, Hongo Bunkyo-Ku, Tokyo 113-8655, Japan. · Sleep Med. · Pubmed #14592281 No free full text.

Abstract: OBJECTIVES AND BACKGROUND: Nocturnal apnea and hypoxia are implicated in the pathogenesis of pulmonary and systemic hypertension in obstructive sleep apnea syndrome (OSAS). We have hypothesized that vasodilating factors including nitric oxide (NO) are affected by nocturnal apnea and hypoxia in patients with OSAS. METHOD: We examined the serum level of NO production in 24 patients with OSAS (mean age 54.2+/-7.9 years) and 24 age-matched control subjects (53.4+/-8.1 years) and tested the effects of oxygen administration on the production of NO in the patients. RESULTS: The serum level of nitrite/nitrates (NO(x)), which are stable metabolites of NO, was lower in patients with OSAS than in control subjects. Administration of 1-2 l/min of oxygen during night increased the patients' NO(x) level from 35.6+/-7.3 to 57.8+/-11.6 microM. Compressed air administration did not affect the NO(x) level in the patients. CONCLUSION: These results indicate that systemic NO production is impaired in OSAS patients, possibly due to nocturnal hypoxia.

Ogihara T, Morimoto S, Okaishi K, Hiwada K, Matsuoka H, Matsumoto M, Takishita S, Shimamoto K, Shimada K, Abe I, Kohara K, Ouchi Y. · Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan. · Hypertens Res. · Pubmed #11924729 links to  free full text

Abstract: A questionnaire survey was administered to Japanese clinical specialists in hypertension in order to gauge their opinions on the 1999 revised version of the Guidelines for Hypertension in the Elderly prepared by the Comprehensive Research Project on Aging and Health of the Ministry of Health and Welfare. Out of 162 council members of the Japanese Society of Hypertension, 122 (75%) replied. The majority (93%) of respondents approved of the guidelines in general, and 72% of them approved of the age-related setting of a therapeutic goal for blood pressure. Sixty-five percent of respondents selected long-acting Ca antagonists, ACE inhibitors and low-dose diuretics as first-line agents for hypertension without complications in the elderly. The results of the questionnaire survey should be reflected in the next version of the guidelines.

Kojima T, Akishita M, Iijima K, Eto M, Ouchi Y. · No affiliation provided · J Am Geriatr Soc. · Pubmed #19016956 No free full text.

This publication has no abstract.

Yamamoto H, Teramoto S, Yamaguchi Y, Ouchi Y. · Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. · Hypertens Res. · Pubmed #18250556 No free full text.

Abstract: Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress and oxidative stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients as compared to an age and body mass index (BMI)-matched control group and an age-matched, but normal-BMI control group. We further hypothesized that nasal continuous positive airway pressure (nCPAP) treatment may decrease OSAS-induced hypoxic stress, oxidative stress and ADM levels. To examine these hypotheses, we measured circulating ADM and reactive oxygen species (ROS) from leukocytes before and after nCPAP therapy in OSAS patients. The circulating levels of ADM and amount of ROS in untreated OSAS patients were significantly greater than those in the controls. No differences in ADM levels were found between the increased-BMI controls and normal-BMI controls. We observed that nCPAP treatment decreased sleep apneas, nocturnal oxyhemoglobin desaturation, the circulating ADM, and ROS production by leukocytes in OSAS patients. The ADM levels were associated with the magnitude of oxyhemoglobin desaturation rather than the number of sleep apneas. These observations suggest that nCPAP therapy could reduce OSAS-induced nocturnal hypoxemia, generation of ROS, and ADM in patients with OSAS.