ENDOTHELIAL-DEPENDENT VASCULAR EFFECTS OF INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I IN THE PERFUSED RAT MESENTERIC-ARTERY AND AORTIC RING

Insulin and insulin-like growth factor I (IGF-I) exhibit vasoactivity. To examine the role of the endothelium in mediating the vascular resp onses to insulin and IGF-I, we exposed both isolated intact rat mesent eric arteries and rat aortic rings to these growth factors in the pres ence and absence of endothelium. Perfusion of rat mesenteric arteries with insulin, IGF-I, or IGF-LT resulted in the potentiation of arginin e vasopressin (AVP)-induced vasoconstriction. Of these growth factors, IGF-I was the most potent, with a significant effect at 0.6 nM and ma ximal effects at 6.0 nM, followed by IGF-II and insulin. Endothelial d enudation or addition of cycloheximide prevented the growth-factor eff ects. Tissue cGMP levels in the mesenteric artery were minimally affec ted by growth factors. Insulin and IGF-I vascular effects were not inh ibited by BQ123, an endothelin (ET) antagonist that blocked ET-1 enhan cement of AVP response. Perfusion of mesenteric arteries with IGF-I fo r 1 h did not alter vessel ET-1 or ET-1 mRNA contents. Addition of ind omethacin markedly inhibited the IGF-I effect on AVP contraction. Thus , the mesenteric vascular effect of insulin and IGF-I is not associate d with ET-1 release but appears to link to an increased release of an endothelial-derived contracting factor or the decreased production of an endothelial-derived relaxing factor from the cyclooxygenase pathway . In contrast to their action in the mesenteric artery, insulin (excee ding 100 nM) and IGF-I (1-30 nM) attenuated AVP- and norepinephrine-in duced contraction in rat aortic rings. Endothelial-denudation abolishe d this effect. L-N-g monomethyl arginine markedly reduced insulin and IGF-I responses in the aortic rings, suggesting involvement of endothe lial nitric oxide production. Furthermore, IGF-I moderately increased tissue cGMP levels in the rings. These results suggest that the vascul ar effects of insulin and IGF-I are vessel-specific and mediated by th e endothelium, possibly via IGF-I receptors.