Role of endogenous adenosine as a modulator of the renin response to salt restriction

Numerous studies indicate that exogenous adenosine can inhibit renin release. However, the hypothesis that endogenous adenosine functions to restrain the renin response to physiological and/or pharmacological stimuli remains untested. To address this hypothesis, we examined the effects of a novel adenosine receptor antagonist, 1,3-dipropyl-8-para-sulfophenylxanthine (DPSPX), on renin release in rats on a normal versus a low salt diet. DPSPX did not affect renal blood flow, glomerular filtration rate, filtration fraction, urine volume, or sodium excretion in rats on either a normal or low salt diet. In contrast, in rats on a low salt diet, DPSPX significantly increased arterial and renal venous plasma renin activity and the gradient of plasma renin activity across the kidney. DPSPX did not alter these indices of renin release in rats on a normal salt diet. These data support the hypothesis that endogenous adenosine functions to restrain the renin response to salt depletion. Finally, if these findings are applicable to man, caffeine consumption could account for the variable antihypertensive effect of a low salt diet.