Renin-angiotensin system inhibition reduces glycine-induced glomerular hyperfiltration in conscious rats.
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)
Wang
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Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Brooks
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DP
D000179:Acrylates / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004656:Enalapril / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005998:Glycine / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013876:Thiophenes
D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan; D004656:Enalapril; D005998:Glycine