| Co-Investigator(Kenkyū-buntansha) |
SASAGAWA Isoji Department of Urology, School of Medicine, Yamagata University, Lecturer, 医学部, 講師 (80196146)
KUBOTA Yoko Department of Urology, School of Medicine, Yamagata University, Associate Professor, 医学部, 助教授 (60125763)
鈴木 仁 山形大学, 医学部, 講師 (30179238)
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| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Research Abstract |
Two-kidney-one, one-clip (2K-1C) rats were treated with splan-chnicotomy, beta-aminopropionitrile (collagen inhibitor), or captopril (angiotensin converting enzyme inhibitor) in the acute or chronic hypertensive phase. 3H-proline was injected into rats, and incorporation of 3H-proline into vascular collagen, non-collagenous protein and elastin were counted. The plasma level of the renin-angiotensin (R-A) system was assayed. In the acute phase of 2K-1C hypertensive rats whose R-A system was enhanced, captopril treatment further enhanced PRA and angiotensin I and suppressed angiotensin II while reducing blood pressure. Synthesis of the vascular protein was almost identical.
In the chronic phase of 2K-1C hypertensive rats whose R-A system was within normal limits, increased incorporation rates of 3H-proline into non-collagenous protein or collagen of mesenteric arteries were decreased by splanchnicotomy or beta-aminopropionitrile and hypertension was lowered. Captopril failed to reduce pro
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tein synthesis. Thus, an enhanced R-A system participates in the pathogenesis of the acute phase of 2K-1C hypertension while increased non-collagenous protein and collagen syntheses of small arteries appear to play some role in the etiology of chronic phase of hypertension. In another experiment, high level of monoamines, such as dopamine (DA), DPAC and HVA enhanced synpathetic nerve system which resulted in hypertension in acute phase of 2K-1C, but not in chronic phase of 2K-1C.
In clinical study we analyzed 99 patients with renovascular hypertension. Evidence has been presented that : (1) for patients with fibromuscular dysplasia and those with aortitis the mean age of cured patients was younger than non-cured patients and the preoperative hypertensive period of the former patients was shorter than the latter patients, but as for the patients with atherosclerosis, there were no significant differences in these variables among cured, alleviative and non-cured groups, (2) for the affected renal arteries, lesions of bilateral renal artery and aorta or lesions located at extrarenal and intrarenal arteries were difficult to be cured in any histological vascular forms, (3) for the patients with fibromuscular dysplasia, improvement of hypertension was achieved more frequently than those with atherosclerosclerosis. Similar result was obtained in the upright posture test in lesser extent, but a almost useless in patients with aortitis.
These results indicate that enhenced R-A system still appears to play some role for sustaining hypertension in patients with fibromuscular dysplasia and those with atherosclerosis, but other factors responsible for maintenance of hypertension must be considered in patients with aortitits whose preoperative hypertensive period is long. Less
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