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 regulation of blood pressure and blood flow remains unknown. This study investigated 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 common iliac artery, left renal artery, and the superior mesenteric artery, and used to measure blood flow. IGF-I (2.6 micrograms, 5.1 or 10.3 nmol/animal 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 pressure (MAP) that continued to decline throughout the 60-min experimental 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 after 60 min. A smaller dose of IGF-I (2.6 nmol) did not significantly decrease the blood glucose but resulted in a slight but significant decrease 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 superior mesenteric vessels, measured as vascular conductance. IGF-I (5.1 and 2.6 nmol) increased preferentially renal vascular conductance. Preinfusion with L-NAME, a nitric oxide inhibitor, inhibited the effects of IGF-I on flow. We conclude that IGF-I can selectively dilate vascular beds leading to a decrease in blood pressure and that the response to IGF-I is mediated by nitric oxide.
Pete
G
G
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Hu
Y
Y
Walsh
M
M
Sowers
J
J
Dunbar
J C
JC
D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate; D007083:Iliac Artery / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000502:physiology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester