Objective. To 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 B2 receptor. Design. Male diabetic Wistar rats were randomly allocated to receive no treatment, the angiotensin converting enzyme inhibitors perindopril or ramipril, the AT1 receptor blocker ZD7155, the bradykinin B2 receptor blocker Hoe140, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine-methyl ester, concomitant administration of perindopril plus subcutaneous Hoe140, perindopril plus N(G)-nitro-L-arginine, or ramipril plus Hoe140 (Hoe140 administered via an Alzet mini-osmotic pump). Methods. After 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 AT1 receptor 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 Hoe140, administered either subcutaneously or via a mini-osmotic pump, or of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine attenuated the effect of the angiotensin converting enzyme inhibitor on the mesenteric vascular weight and wall:lumen area ratios. Treatment with Hoe140 or N(G)-nitro-L-arginine alone affected none of these parameters. Conclusion. The 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.
- Angiotensin converting enzyme inhibitors
- Angiotensin II
- Mesenteric vessels
- Nitric oxide
- Vascular hypertrophy