Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action
Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action
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DOI：
10.1097/00004872-199816060-00010
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发表时间：
1998-06-01
影响因子：
4.9
通讯作者：
Cooper, ME
中科院分区：
文献类型：
--
作者：
Cao, ZM;Hulthén, UL;Cooper, ME
目的探讨血管紧张素II、缓激肽和钙依赖通路在实验性糖尿病肠系膜血管肥大发生中的作用。设计链脲佐菌素诱导的糖尿病大鼠，随机分为4组，每组24周：不治疗；降压剂量雷米普利；雷米普利+缓激素2型受体阻滞剂icatibant；icatibant；小剂量雷米普利；血管紧张素II 1型受体拮抗剂valsartan；二氢吡啶钙拮抗剂拉西地平；非二氢吡啶钙拮抗剂米贝地平。结果大剂量雷米普利、雷米普利单独或与卡替本联合应用、Valsartan、小剂量雷米普利或钙拮抗剂拉西地平和米贝弗地尔均可降低实验性糖尿病大鼠的血压和肠系膜动脉壁/腔比，小剂量雷米普利或钙拮抗剂拉西地平和米贝弗地尔均可使肠系膜动脉壁/腔比降低，但对血压无影响。结论阻断血管紧张素Ⅱ依赖和钙依赖途径均可减轻实验性糖尿病肠系膜血管肥大。此外，这些抗高血压药物的抗营养作用可能不依赖于它们的降压作用。(C)1998年利平科特-乌鸦出版社。
Objectives To investigate the relative roles of angiotensin II, bradykinin, and calcium-dependent pathways in the genesis of mesenteric Vascular hypertrophy in experimental diabetes.Design Streptozotocin-induced diabetic Sprague-Dawley rats were randomly allocated to these treatments for 24 weeks: no treatment; ramipril at a hypotensive dose; ramipril plus the bradykinin type 2 receptor blocker icatibant; icatibant alone; ramipril at a low dose; the angiotensin II type 1 receptor antagonist, valsartan; the dihydropyridine calcium antagonist, lacidipine; and the nondihydropyridine calcium antagonist mibefradil.Methods Systolic blood pressure was serially measured every 4 weeks by tail-cuff plethysmography. We assessed the vascular architecture in sections of mesenteric arteries obtained after in-vivo perfusion, which were stained with an antibody to alpha-smooth muscle actin.Results Both blood pressure and the mesenteric arterial wall:lumen ratio were reduced by administration of ramipril, at the high dose, either alone or in combination with icatibant, and also by valsartan, Treatment either with the low dose of ramipril or with the calcium antagonists lacidipine and mibefradil was associated with a decrease in the wall:lumen ratio of the mesenteric arteries without influencing blood pressure.Conclusions These findings demonstrate that blockade both of angiotensin II-dependent and of calcium-dependent pathways attenuates mesenteric vascular hypertrophy in experimental diabetes. Furthermore, the antitrophic effects of these antihypertensive agents may be independent of their hypotensive effects. (C) 1998 Lippincott-Raven Publishers.