ROLE OF BRADYKININ IN INSULIN SENSITIVITY AND FLOOD PRESSURE REGULATION DURING HYPERINSULINEMIA

The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide i n glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin an tagonists, indomethacin or N-omega-nitro-L-arginine methyl ester, conc urrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykini n inhibition dramatically reduced glucose uptake and insulin sensitivi ty index during both the lower and higher insulin infusion rates to 30 % and 32%, respectively, of values observed in control rats. Inhibitio n of prostaglandins or nitric oxide did not alter glucose metabolism i n these rats. Blood pressure remained unchanged in the control group t hroughout the clamp but increased significantly in rats submitted to i nhibition of bradykinin, prostaglandins, or nitric oxide, suggesting t hat these vasodilator systems tend to counteract the hypertensive effe ct of hyperinsulinemia. The counterregulatory component attributable t o bradykinin was about twice as great as that attributable to nitric o xide. These findings suggest that insulin infusion in normotensive Wis tar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostag landins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition signi ficantly reduces insulin sensitivity and allows blood pressure to rise .