INSULIN-LIKE GROWTH-FACTOR-I DECREASES MEAN BLOOD-PRESSURE AND SELECTIVELY INCREASES REGIONAL BLOOD-FLOW IN NORMAL RATS

The insulin-like growth factor-I (IGF-I) and its receptors are widely distributed in peripheral vascular tissue, yet their role in the regul ation of blood pressure and blood flow remains unknown, This study inv estigated the effect of IGF-I on blood pressure and selected regional blood flow in normal Wistar rats anesthetized with chloralose/urethane . The femoral artery was cannulated and used to monitor arterial blood pressure, Electromagnetic flow probes were placed around the left com mon iliac artery, left renal artery, and the superior mesenteric arter y, and used to measure blood flow, IGF-I (2.6 mu g, 5.1 or 10.3 nmol/a nimal iv) was injected as a bolus into the femoral vein, Following the injection of IGF-I (10.3 nmol), we observed a significant decrease of plasma glucose (57%) and a significant decrease of mean arterial pres sure (MAP) that continued to decline throughout the 60-min experimenta l period, IGF-I (5.1 nmol) significantly decreased blood glucose by 44 % and decreased the MAP by 14% with a nadir at 15 min and recovery aft er 60 min, A smaller dose of IGF-I (2.6 nmol) did not significantly de crease the blood glucose but resulted in a slight but significant decr ease in MAP, The heart rate was increased by 10.3 and 5.1 but not 2.5 nmol of IGF-I, IGF-I (10.3 nmol) was associated with regional vascular responses with a preferential increase in flow of the iliac and super ior mesenteric vessels, measured as vascular conductance, IGF-I (5.1 a nd 2.6 nmol) increased preferentially renal vascular conductance. Prei nfusion with L-NAME, a nitric oxide inhibitor, inhibited the effects o f IGF-I on flow, We conclude that IGF-I can selectively dilate vascula r beds leading to a decrease in blood pressure and that the response t o IGF-I is mediated by nitric oxide.