EFFECTS OF INSULIN-LIKE-GROWTH-FACTOR-I ON THE RENAL JUXTAMEDULLARY MICROVASCULATURE

To characterize the effects on the rat renal preglomerular microvascul ature of insulinlike growth factor I (IGF-I), experiments were perform ed using the in vitro blood-perfused juxtamedullary nephron preparatio n. IGF-I induced a reversible vasodilation of pre- but not postglomeru lar microvessels in a dose-dependent manner (10(-9) - 10(-7) M). The I GF-I-induced vasodilation was similar in all preglomerular vascular se gments: interlobular artery, 11.5 +/- 1.2% of control (n = 16); mid-af ferent arterioles, 11.6 +/- 1.7% (n = 24); and juxtaglomerular afferen t 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 inh ibited the vasodilatory response to IGF-I. IGF-I induced a rapid incre ase of NO concentration in intact renal microvessels, monitored by a N O-selective voltametric microelectrode. Pretreatment with the cyclooxy genase inhibitor indomethacin (10(-5) M) not only abrogated the IGF-I- induced dilation, but, moreover IGF-I elicited a small but significant (similar to 10%) vasoconstriction in all preglomerular vessels. These results indicate that the renal vascular effects of IGF-I involve act ivation oi two endogenous vasodilators (NO and vasodilatory prostaglan dins). In addition, IGF-I may also release an undefined vasoconstricto r.