Angiotensin II control of the renal microcirculation in rats with reduced renal mass

Abstract

It has been suggested that angiotensin II (ANG II) activation after renal ablation contributes to the altered glomerular dynamics and proteinuria that characterizes this model of chronic renal failure. In the present study, male Munich-Wistar rats underwent 75% renal ablation (Nx group). Two weeks later, micropuncture studies were performed in sham-operated rats (sham group) and Nx group rats during intravenous infusion of either a vehicle or two ANG II inhibitors, namely [Sar1, Ala8]ANG II or MK-421 administered at a rate of 0.3 and 1 mg.kg body wt-1.h-1, respectively. Acute ANG II inhibition in sham group had no effect on mean arterial pressure (MAP), glomerular dynamics, or proteinuria. In contrast, in Nx group ANG II inhibition lessened glomerular hypertension (from 64.7 +/- 1.0 to 55.4 +/- 1.7 mmHg, P less than 0.0001) the result of postglomerular vasodilation (P less than 0.01), normalized the glomerular ultrafiltration coefficient (from 0.038 +/- 0.002 to 0.005 +/- 0.002 nl.s-1.mmHg-1, P less than 0.0001), and attenuated proteinuria (from 42.1 +/- 6.5 to 28.1 +/- 5.4 micrograms/min, P less than 0.01). MAP, single-nephron GFR and plasma flow were unaffected. These results suggest that ANG II activity is enhanced in nephrectomy, contributing in a major way to altered glomerular dynamics and proteinuria.