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Renin-angiotensin system inhibition reduces glycine-induced glomerular hyperfiltration in conscious rats

YX Wang and DP Brooks

Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.

It has been reported that high protein intake or amino acid infusion- induced glomerular hyperfiltration are accompanied by an elevation of plasma renin activity and renal renin mRNA. We therefore investigated the effect of inhibition of the renin-angiotensin system by SK&F 108566, a novel, nonpeptide angiotensin II (AII) receptor antagonist, or by enalapril, an angiotensin converting enzyme inhibitor, on glycine- induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate clearances in conscious chronically instrumented rats. Glycine infusion (3.7 mg/min i.v.; n = 8) significantly increased GFR by 27% (from 1.09 +/- 0.53 to 1.38 +/- 0.08 ml/min.100 g), ERPF by 22% (2.96 +/- 0.30 to 3.61 +/- 0.32 ml/min.100 g) and significantly decreased effective renal vascular resistance by 22% [from 25.4 +/- 2.9 to 20.8 +/- 2.5 mm Hg/(ml/min.100 g)]. SK&F 108566 (30 micrograms/kg.min) or enalapril (1 mg/kg), at doses which inhibited the pressor effects of AII or AI, respectively, but had no significant influence on base-line GFR and ERPF, significantly attenuated the glycine-induced glomerular hyperfiltration and hyperemia. In the presence of SK&F 108566 or enalapril, glycine resulted in only small, statistically insignificant changes in GFR (from 1.07 +/- 0.03 to 1.10 +/- 0.04 and from 1.19 +/- 0.03 to 1.21 +/- 0.08 ml/min.100 g, respectively), ERPF (from 3.27 +/- 0.21 to 3.53 +/- 0.26 and from 3.57 +/- 0.11 to 3.41 +/- 0.38 ml/min.100 g, respectively) and effective renal vascular resistance [from 21.2 +/- 1.9 to 19.2 +/- 1.6 and from 18.4 +/- 0.9 to 20.2 +/- 2.2 mm Hg/(ml/min.100 g], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 261, Issue 1, pp. 96-100, 04/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.