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.
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, U.K.
A A
AA
el Sayed
J
J
Haylor
A M
AM
el Nahas
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