Amino acids induce renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism.
Renal vasodilatation regularly accompanies protein feeding and amino acid infusions, but the mechanism is unknown. The effects of several different amino acids on renal hemodynamics were studied in the isolated rat kidney, perfused with glucose as the only other substrate. Addition of amino acids produced a dose-dependent, brisk, and sustained decrease in renal vascular resistance (by 5-35%) without change in glomerular filtration rate (GFR). The vasodilatation was associated with a parallel increase in O2 consumption (increases QO2). The effect was most marked with amino acids actively metabolized by the kidney, such as glutamine (at 2 mM), but was seen with most amino acids at 8 mM. The amino acid analogues alpha-aminobutyrate, taurine, and cycloleucine, cotransported with sodium but not metabolized, did not cause significant vasodilatation or increases QO2. Blocking active transport with ouabain blunted the amino acid-induced vasodilatation and increases QO2. Similar resistance to amino acids was produced by halting GFR with hyperoncotic medium. Restoration of GFR by increasing perfusion pressure in the presence of hyperoncotic medium reestablished amino acid-induced vasodilatation and increases QO2. Furosemide did not block the vasodilatory response. Inhibition of mitochondrial respiration by antimycin blocked both vasodilatation and increases QO2, but rotenone blockade could be bypassed by succinate or glutamine. Amino acids have a direct vasodilating action on isolated kidneys probably related to their role as metabolic substrates and linked to an increase in renal O2 consumption.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000596:Amino Acids