2006 Fiscal Year Final Research Report Summary
Role of Angiotension and CD36 Expression in Multiple Risk Factors for Atherosclerosis
| Project/Area Number |
17590705
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
NAKAMURA Tetsuya Gunma University, Clinical Investigation and Research Unit, Associate Professor, 医学部, 助教授 (10272238)
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| Co-Investigator(Kenkyū-buntansha) |
KURABAYASHI Masahiko Gunma University Graduate School of Medicine, Department of Medicine and Biological Science, Professor, 大学院医学系研究科, 教授 (00215047)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Hypertension / Insulin resistance / Angiotensin converting enzyme / atherosclerosis |
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| Research Abstract |
OBJECTIVE : Diiihydropyridine calcium channel blockers (CCB) can prevent the CV events in diabetes. Angiotensin II plays a key role in pathobiological events that lead to vascular disease. The present study examined the long-term effects of CCB and angiotensin II receptor blocker on the cardiovascular protective effects in hypertension.
METHODS and RESULTS : Thirty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rates, a model of diabetes with elevated BP, and normal control (Long Evans Tokushima Otsuka : LETO) rats were fed standard chow or chow containing CCB azelnidipine, 0.4 mg/g food (n=15 in each group) for 2 weeks. Angiotensin enzyme (ACE) mRNA in both renal cortex and medulla of OLETF was reduced compared to LETO rats, and further suppressed by azelnidipine. The renal cortical mineralocorticoid receptor (MCR) mRNA in OLETF was higher than in LETO, and reduced significantly by azelnidipine. MCR mRNA in the renal medulla did not differ significantly between 2 strains, and was unaltered by azelnidipine in either strain.
In 46 patients with hypertension, the pulse wave velocity between the brachium and ankle (baPWV) was measured before and 24 weeks after the treatment with valsartan 40 to 160 mg/day. Systolic and diastolic blood pressures were decreased from 155±3 to 140±3 and from 90±2 to 82±2 mmHg, respectively. The baPWV also decreased from 1853±49 cm/sec to 1682 ±52 cm/sec.
CONCLUSION : We demonstrated that azelnidipine normalized the enhanced renal cortical expression of MCR mRNA and reduced renal ACE mRNA in diabetic rats. This is the first report providing that L-type CCB can down-regulated renal expression of ACE and MCR mRNA. We conclude that the treatment effect of valsartan reduces arterial stiffness regardless of baseline blood pressure. Blood pressure reduction alone does not appear to account entirely for the benefits of valsartan therapy on arterial stiffness.
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