Adenosinergic modulation of the imidazoline I1-receptor-dependent hypotensive effect of ethanol in acute renal failure

We reported that inhibition of central sympathetic pools of imidazoline I1 receptors abolishes the hypotensive effect of ethanol in rats with glycerol-induced acute renal failure (ARF). This study investigated whether adenosine receptors modulate the ethanol-I1-receptor interaction. The effect of selective blockade of adenosine A1, A2A, or A2B receptors on hemodynamic responses to ethanol in the absence and presence of the I1-receptor agonist moxonidine was determined in ARF rats. Ethanol (1 g/kg i.v.) decreased and increased blood pressure (BP) and heart rate (HR), respectively. Pretreatment with moxonidine abolished the hypotensive but not the tachycardic effect of ethanol. The hypotensive effect of ethanol remained unaltered after selective blockade of A1, A2A, or A2B receptors with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 8-(3-chlorostyryl) caffeine (CSC) and alloxazine, respectively. Neither was ethanol hypotension affected after inhibition of adenosine uptake by dipyridamole (DPY). Alternatively, the ability of moxonidine to abolish ethanol hypotension was still evident in presence of alloxazine whereas it disappeared or weakened in rats pretreated with CSC and DPCPX, respectively. These findings implicate adenosine A2A receptors in the moxonidine-evoked inhibition of the hypotensive action of ethanol. A modulatory role for adenosine A1 site in the ethanol-I1-receptor interaction is also possible through as yet unidentified mechanism.

► Adenosinergic modulation of the hypotensive effect of ethanol was investigated. ► Activation of A2AAR but not A2BAR is essential for ethanol hypotension. ► A role for A1AR in the I1-receptor-ethanol hemodynamic interaction is also possible.