Renal effects of selective adenosine receptor agonists in anesthetized rats

Exogenous adenosine affects renal hemodynamics, renal tubular transport processes, and the secretion of renin. However, adenosine is not a selective agonist; it activates both A1 and A2 cell-surface receptors and it binds to an intracellular P-site that inhibits adenylate cyclase activity. Recent in vitro studies have suggested that activation of A1- and A2- adenosine receptors results in opposite effects on renin secretion. The purpose of these experiments was to examine the renal effects of A1- and A2-adenosine receptor agonists in vivo. 5'-N-ethylcarboxamide adenosine (NECA), 2-chloroadenosine (2-CLA), and N6-cyclohexyladenosine (CHA) were infused intravenously at rates that produced comparable decreases in systemic arterial blood pressure. All three of these adenosine analogues produced comparable decreases in para-aminohippurate (PAH) and inulin clearances and in Na and K excretion rates. CHA, an A1-selective agonist, markedly decreased plasma renin concentration (PRC), whereas NECA, an A2-selective agonist, markedly increased PRC; 2-CLA, a nonselective agonist, produced a smaller increase in PRC. Taken together, these results suggest that occupation of A1- and A2-receptors inhibits and stimulates renin secretion in vivo, independently of the effects of these adenosine receptor agonists on arterial blood pressure, renal hemodynamics, and tubular Na and K transport.