Effects of insulin-like growth factor I on the renal juxtamedullary microvasculature

To characterize the effects on the rat renal preglomerular microvasculature of insulin-like growth factor I (IGF-I), experiments were performed using the in vitro blood-perfused juxtamedullary nephron preparation. IGF-I induced a reversible vasodilation of pre-but not postglomerular microvessels in a dose-dependent manner (10^-9-10^-7 M). The IGF-I-induced vasodilation was similar in all preglomerular vascular segments: interlobular artery, 11.5 ± 1.2% of control (n = 16); mid-afferent arterioles, 11.6 ± 1.7% (n = 24); and juxtaglomerular afferent segments, 16.1 ± 2.8% (n = 19). Renal autoregulatory capacity was not reduced by IGF- I. Pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-L- arginine methyl ester (10^-4 M) completely inhibited the vasodilatory response to IGF-I. IGF-I induced a rapid increase of NO concentration in intact renal microvessels, monitored by a NO-selective voltametric microelectrode. Pretreatment with the cyclooxygenase inhibitor indomethacin (10^-5 M) not only abrogated the IGF-I-induced dilation, but, moreover, IGF- I elicited a small but significant (~10%) vasoconstriction in all preglomerular vessels. These results indicate that the renal vascular effects of IGF-I involve activation of two endogenous vasodilators (NO and vasodilatory prostaglandins). In addition, IGF-I may also release an undefined vasoconstrictor.