Concentration dependency of the renal vascular and renin secretory responses to adenosine receptor agonists.
Exogenous adenosine inhibits renin secretion and can either vasoconstrict or vasodilate the renal vasculature in vivo. In previous experiments, we found that micromolar concentrations of N6-cyclohexyl adenosine and 5'-N-ethylcarboxamide adenosine, analogs which are relatively selective for A1 and A2 adenosine receptors, respectively, tended to have opposite effects on both afferent arteriolar resistance and renin secretory rate in isolated rat kidneys perfused at constant pressure. Because the affinities of A1 and A2 receptors differ considerably, the purpose of the present experiments was to determine the concentration dependencies of the renal hemodynamic (perfusion pressure or perfusate flow, glomerular filtration rate, filtration fraction) and the renin secretory effects of adenosine, N6-cyclohexyl adenosine and 5'-N-ethylcarboxamide adenosine. Both the renovascular and the renin secretory effects of CHA were biphasic; at submicromolar concentrations, total and afferent arteriolar resistances were increased and renin secretion was inhibited. At higher concentrations, these effects were reversed or abolished. 5'-N-Ethylcarboxamide adenosine and adenosine decreased total and segmental (afferent and efferent) resistances and stimulated renin secretion. Taken together, the results are consistent with the suggestions that A1 and A2 receptors mediate inhibition and stimulation of renin secretion, that afferent arteriolar A1 and A2 receptors mediate constriction and dilation and that efferent arteriolar A2 receptors mediate dilation.
Murray
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Churchill
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PC
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply*; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011983:Receptors, Purinergic; D012083:Renin / Q000097:blood*; D014655:Vascular Resistance / Q000187:drug effects
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D012083:Renin; D000241:Adenosine; D011188:Potassium