INSULIN-LIKE GROWTH-FACTOR-I PRODUCES RENAL HYPERFILTRATION BY A KININ-MEDIATED MECHANISM

Insulin-like growth factor-I (IGF-I) infusion into rats and humans red uces renal vascular resistance and raises glomerular filtration rate ( GFR) and renal plasma flow (RPF). To investigate whether kinins mediat e the renal vasodilatory effects of IGF-I, we infused rats with IGF-I alone or in the presence of a B-2 kinin receptor antagonist. Left kidn ey GFR, RPF, and kinin excretion were measured during infusion of vehi cle and subsequently during 60-min infusion ofIGF-I or IGF-I plus kini n antagonist. IGF-I was given as a bolus (150 mu g/kg body wt), follow ed by infusion at a rate of 8.3 mu g.kg(-1).min(-1) for 60 min. The ki nin antagonist was infused at a dose of 1 mu g.kg(-1).min(-1) for 60 m in before the start of IGF-I infusion. GFR and RPF increased significa ntly after IGF-I infusion was begun, from baseline levels of 1.70 +/- 0.12 and 6.21 +/- 0.34 to 2.12 +/- 0.11 and 7.98 +/-: 0.29 ml/min, res pectively, at 20 min (P < 0.001). This effect was maintained throughou t 60 min of infusion. The increase in GFR and RPF was associated with a marked rise in urinary kinin excretion, from a baseline of 8.51 +/- 6.7 to 24.7 +/- 6.7 pg/min at 20 min and 40.3 +/- 10.4 pg/min at 40 mi n (P < 0.001). Pretreatment with the kinin receptor antagonist blocked the rise in GFR and RPF in response to IGF-I. These data suggest that the renal vasodilatory effect of IGF-I is mediated by kinins.