Mediators of the direct effects of amino acids on the rat kidney.
1. The response of the isolated rat kidney to a mixed amino acid solution was examined in the presence of three renal autacoid inhibitors, indomethacin (a cyclo-oxygenase inhibitor), sulpiride (a dopamine antagonist) and L-nitroarginine methyl ester (an inhibitor of nitric oxide synthesis). 2. Increasing the concentration of the mixed amino acid solution perfusing the kidney from 2 to 8 mmol/l (n = 6) produced a sustained increase in renal perfusate flow (P less than 0.01) and reversed the time-dependent fall in [14C]inulin clearance (P less than 0.01) demonstrated in kidneys perfused with 2 mmol/l mixed amino acids alone. A significant increase in the fractional sodium reabsorption and decrease in the fractional albumin excretion was also observed. 3. Indomethacin (10(-4) mol/l, n = 6) produced partial (50%) inhibition of the effect of mixed amino acids on [14C]inulin clearance, but did not influence their ability to increase renal perfusate flow. 4. Sulpiride (0.7 mumol min-1 kg-1, n = 6) produced partial inhibition of the effect of mixed amino acids on both [14C]inulin clearance and renal perfusate flow by 60% and 50%, respectively. Sulpiride also entirely inhibited the reduction in fractional albumin excretion. 5. L-Nitroarginine methyl ester (10(-4) mol/l, n = 6) completely inhibited the effect of mixed amino acids on [14C]inulin clearance, but did not inhibit the increase in renal perfusate flow, even though the basal vascular resistance was markedly enhanced. L-Nitroarginine methyl ester also inhibited the increase in fractional sodium reabsorption produced by the mixed amino acids. 6. It is concluded that prostaglandins, dopamine and nitric oxide may all have a role to play in the direct effect of mixed amino acids on renal function. This does not, however, preclude further modification by additional stimuli generated in vivo.
el Sayed
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AA
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, U.K.
Haylor
J
J
el Nahas
A M
AM
D000418:Albumins / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012898:Autacoids / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D018492:Dopamine Antagonists; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009924:Organ Culture Techniques; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology*
D000418:Albumins; D000596:Amino Acids; D012898:Autacoids; D016861:Cyclooxygenase Inhibitors; D018492:Dopamine Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D013469:Sulpiride; D001120:Arginine; D012964:Sodium; D007213:Indomethacin