Adenosinergic Modulation Of The Imidazoline I1‐Receptor‐Dependent Hypotensive Effect Of Ethanol In Acute Renal Failure

Abstract

We recently reported that ethanol lowers blood pressure (BP) in rats with acute renal failure (ARF) via facilitation of sympathoinhibitory pathways of central imidazoline I1‐receptors. This study investigated whether adenosine receptor subtypes modulate the ethanol‐I1‐receptor interaction. The effect of selective blockade of adenosine A1, A2A, or A2B receptors on hemodynamic responses to consecutive administration of moxonidine, I1‐receptor agonist, and ethanol was determined in the glycerol model (10 ml/kg, i.m.) of ARF. Ethanol (1 g/kg i.v.) elicited significant decreases and increases in BP and heart rate (HR), respectively, in ARF rats. Prior exposure to moxonidine abolished the hypotensive but not the tachycardic effect of ethanol. The ability of moxonidine to abolish ethanol hypotension disappeared after selective blockade of adenosine A1 or A2A receptors with 8‐Cyclopentyl‐1,3‐dipropylxanthine and 8‐(3‐chlorostyryl) caffeine, respectively. In contrast, the moxonidine‐ethanol interaction was not affected in presence of alloxazine, a selective A2B antagonist or 8‐phenyltheophylline, a nonselective adenosine receptor antagonist. These findings suggest that alterations caused by moxonidine in adenosine A1 and A2A receptor signaling function to offset the I1‐receptor‐dependent hypotensive action of ethanol in ARF rats.