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Title: Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action.
Austin Authors: Cao, Zemin;Hulthén, U L;Allen, Terri J;Cooper, Mark E
Affiliation: Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West, Victoria, Australia
Issue Date: 1-Jun-1998
Publication information: Journal of Hypertension; 16(6): 793-9
Abstract: To investigate the relative roles of angiotensin II, bradykinin, and calcium-dependent pathways in the genesis of mesenteric vascular hypertrophy in experimental diabetes.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.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.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.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.
Gov't Doc #: 9663919
Journal: Journal of Hypertension
Type: Journal Article
Subjects: Actins.metabolism
Angiotensin-Converting Enzyme Inhibitors.pharmacology
Blood Pressure.drug effects
Calcium Channel Blockers.pharmacology
Calcium Channels.drug effects.metabolism
Diabetes Mellitus, Experimental.metabolism.pathology.physiopathology
Mesenteric Arteries.drug effects.pathology
Muscle, Smooth, Vascular.drug effects.pathology
Peptidyl-Dipeptidase A.drug effects.metabolism
Random Allocation
Rats, Sprague-Dawley
Appears in Collections:Journal articles

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