INSULIN-LIKE GROWTH-FACTOR-I RESTORES MICROVASCULAR AUTOREGULATION INEXPERIMENTAL CHRONIC-RENAL-FAILURE

Impairment of autoregulation (AR) is associated with accelerated progr ession of chronic renal failure (CRF). As the bioavailability of insul in-like growth factor-I (IGF-I) is low in CRF, we investigated the eff ects of acute luminal application of 10 nM recombinant human IGF-I on AR in juxtamedullary (JM) afferent arterioles (AA) perfused in vitro w ith a blood solution [(similar to 30% hematocrit (HCT)I. Studies were conducted in AA from adult male rats three to four weeks after five-si xths nephrectomy (Nx) by either surgical excision (N = 7) or infarctio n (N = 5) of two thirds of the remnant kidney; controls (N = 6) had sh am surgery. AA from both Nx groups exhibited marked hypertrophy and im paired AR responses (60 to 140 mm HE perfusion pressure), features mor e pronounced in the infarction group. Responses to abluminal acetylcho line (10 mu M) were similar in sham and excision groups but were signi ficantly blunted in the infarction group. All groups vasodilated signi ficantly after Ca-channel blockade (10 mM MnCl2). IGF-I restored AR in AA from both Nx groups (P < 0.05, analysis of variance) while it vaso dilated AA from controls. These results suggest that IGF-I may protect the glomerulus from injury by maintaining autoregulatory control of r enal blood flow, thereby slowing the progression of CRF.