Kinins or nitric oxide, or both, are involved in the antitrophic effects of angiotensin converting enzyme inhibitors on diabetes-associated mesenteric vascular hypertrophy in the rat


    loading  Checking for direct PDF access through Ovid

Abstract

ObjectiveTo determine the roles played by kinins/nitric oxide and angiotensin II in the antitrophic effects of angiotensin converting enzyme inhibitors on mesenteric arteries after 3 weeks of streptozotocin diabetes by using blockers both of the angiotensin II AT1 receptor and of the bradykinin B 2 receptorDesignMale diabetic Wistar rats were randomly allocated to receive no treatment, the angiotensin converting enzyme inhibitors perindopril or ramipril, the AT1 receptor blocker ZD 7155, the bradykinin B 2 receptor blocker Hoe 140, the nitric oxide synthase inhibitor NG- nitro-L-arginine-methyl ester, concomitant administration of perindopril plus subcutaneous Hoe 140, perindopril plus A/G-nitro-L-arginine, or ramipril plus Hoe 140 (Hoe 140 administered via an Alzet mini-osmotic pump)MethodsAfter 3 weeks, the rats were killed, their blood collected and their mesenteric vessels removed. The mesenteric vascular weight was measured and the media wall: lumen area ratio was assessed using quantitative histomorphometric techniques. Results Diabetes was associated with an increase in mesenteric weight and media wall: lumen area ratio. The angiotensin converting enzyme inhibitors, perindopril and ramipril, and the AT1receptor antagonist ZD7155 reduced blood pressure and attenuated vascular weight and media wall: lumen area ratio. Concomitant administration of an angiotensin converting enzyme inhibitor with the kinin antagonist Hoe 140, administered either subcutaneously or via a mini-osmotic pump, or of the nitric oxide synthase inhibitor NG- nitro-L-arginine attenuated the effect of the angiotensin converting enzyme inhibitor on the mesenteric vascular weight and wall: lumen area ratios. Treatment with Hoe 140 or NG- nitro-L-arginine alone affected none of these parameters.ConclusionThe antitrophic effect of angiotensin converting enzyme inhibitors on diabetic mesenteric arteries is mediated by inhibition of angiotensin II and by actions on the kinin-nitric oxide pathway

    loading  Loading Related Articles