Effects of amino acid infusion on renal hemodynamics. Role of endothelium-derived relaxing factor.
Ingestion of protein or intravenous infusion of amino acids acutely elevates glomerular filtration rate (GFR) and renal plasma flow (RPF) by unknown mechanisms. Endothelium-derived relaxing factor (EDRF), now known to be nitric oxide derived from metabolism of L-arginine, participates in local regulation of vascular tone. To investigate the hypothesis that EDRF may participate in the renal vasodilatation and increased GFR after amino acid infusion, we characterized the effect of inhibition of EDRF synthesis with NG-monomethyl L-arginine (LNMMA) on basal renal hemodynamics and the response to infusion of a 10% mixed amino acid solution (1 ml/hr i.v.) in the rat. Renal arterial infusion of LNMMA (500 micrograms/kg/min) resulted in a significant increase in mean arterial pressure, decreases in GFR (20%) and RPF (44%), and a significant increase in filtration fraction. Pretreatment with the angiotensin II receptor antagonist Sar-Gly-angiotensin II did not prevent the increase in blood pressure but blunted the decreases in GFR (11%) and RPF (27%) after LNMMA infusion. Amino acid infusion in the untreated, fasted rat resulted in no change in blood pressure but significant increases in GFR and RPF; these effects were completely inhibited by intrarenal LNMMA but not an equihypertensive intravenous infusion of phenylephrine. In summary, EDRF participates in regulation of basal renal hemodynamics. Furthermore, amino acid-induced hyperfiltration and renal vasodilatation are completely prevented by inhibition of EDRF synthesis. We conclude that EDRF may participate in the renal hemodynamic response to amino acid infusion.
Tolins
J P
JP
Veterans Administration Medical Center, Minneapolis, MN.
Raij
L
L
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D000596:Amino Acids; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine