Role of renal medullary adenosine in the control of blood flow and sodium excretion

This study determined the levels of adenosine in the renal medullary inters titium using microdialysis and fluorescence HPLC techniques and examined th e role of endogenous adenosine in the control of medullary blood flow and s odium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowme try. Analysis of microdialyzed samples showed that the adenosine concentrat ion in the renal medullary interstitial dialysate averaged 212 +/- 5.2 nM, which was significantly higher than 55.6 +/- 5.3 nM in the renal cortex (n = 9). Renal medullary interstitial infusion of a selective Al antagonist, 8 -cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol.kg(-1).min(-1), n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A (2) receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX; 150 pmol.kg(-1 ).min(-1), n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal me dullary interstitial infusion of adenosine produced a dose-dependent increa se in OMBF, IMBF, urine flow and sodium excretion at doses from 3 to 300 pm ol.kg(-1).min(-1) (n = 7). These effects of adenosine were markedly attenua ted by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a sele ctive A(3) receptor agonist, N-6-benzyl-5'-(N-ethylcarbonxamido)adenosine ( 300 pmol.kg(-1).min(-1), n = 6) into the renal medulla had no effect on med ullary blood flows or renal function. Glomerular filtration rate and arteri al pressure were not changed by medullary infusion of any drugs. Our result s indicate that endogenous medullary adenosine at physiological concentrati ons serves to dilate medullary vessels via A(2) receptors, resulting in a n atriuretic response that overrides the tubular A(1) receptor-mediated antin atriuretic effects.