The effect of chronic angiotensin (1-7) treatment on functional response of isolated resistance arteries in diabetic rats

ABSTRACT Objective: Diabetes Mellitus (DM) is an important disease causing cardiovascular morbidity and mortality. Ang (1-7) is an endogenous substance producing stabilizing/protective effects against various harmful effects of Ang II. In this study, the effects of Ang (1-7) treatment on responses to various endogenous vasoactive substances and the mechanisms involved in these effects were investigated in diabetic rat isolated resistance arteries. Method: Wistar rats were seperated into Control, Control + Ang (1-7), DM and DM + Ang (1-7) groups. Ang (1-7) treatment was given 576 µg/kg/day s.c for 4 weeks. Responses of isolated mesenteric artery rings to endogenous vasoconstrictor and vasodilator agents were recorded in wire myograph. Local (mesenteric artery) and systemic (serum) oxidant/antioxidant status was evaluated with TOS and TAS levels. Results: Sensitivity to vasoconstrictor agents increased while responses to endothelium-dependent vasodilators decreased in DM compared to Control groups. Ang (1-7) treatment partially reversed the changes in vascular responses in DM groups. L-NAME incubation in Control groups and SOD incubation in DM groups caused significant decrements and increments, respectively, in vasorelaxant responses to acetylcholine. Incubation of isolated vessels with apamine or caribdotoxin caused similar reductions, whereas those with glibenclamide, 4-AP, indomethacine or catalase no significant changes in responses to acetylcholine in DM and Control groups. Local and systemic oxidant/antioxidant status parameters did not differ significantly between experimental groups. Conclusion: It was concluded that reduction in bioavailability of nitric oxide due to endothelial dysfunction and/or increase in oxidative stress may play a role in alterations in functional responses of resistance arteries in DM, and Ang (1-7) treatment may represent a new therapeutic approach for the endothelial dysfunction in DM. Key words: Diabetes Mellitus, Renin-Angiotensin-Aldosterone System (RAAS), Angiotensin (1-7), wire myograph system, isolated resistance artery