EFFECTS OF SELECTIVE A(1) RECEPTOR BLOCKADE ON GLOMERULAR HEMODYNAMICS - INVOLVEMENT OF RENIN-ANGIOTENSIN SYSTEM

We examined the renal effects of a specific adenosine A(1)-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 mu g.kg(-1).min(-1) iv). Since adenosine is a potent inhibitor of renin release, additional experiments were performed with an angiotensin AT(1)-receptor antagonist (losartan, 10 mg/kg iv). DPCPX alone induced a significant (P < 0.05) decrease in afferent arteriolar resistance (R(A), 1.83 +/- 0.18 to 1.43 +/- 0.06 dyn.s.cm(-5) x 10(10); P < 0.05). This led to a rise in the transcapillary hydraulic pressure difference (Delta P, 35 +/- 1 to 43 +/- 2 mmHg; P < 0.05). Surprisingly, the glomerular capillary ultrafiltration coefficient (K-f) fell(0.101 +/- 0.017 to 0.064 +/- 0.009 nl.s(-1).mmHg(-1), P < 0.05). Additionally, DPCPX infusion resulted in dramatic increases in both urine flow and sodium excretion. With losartan pretreatment, DPCPX did not cause significant changes in R(A) and Delta P. Also, DPCPX increased K-f (0.057 +/- 0.005 to 0.075 +/- 0.008 nl.s(-1).mmHg(-1), P < 0.05). Furthermore, the large DPCPX-induced increases in urine flow and sodium excretion were largely suppressed by pretreatment with losartan. These data indicate that endogenous adenosine plays a significant role in maintaining afferent arteriolar tone and that the renin-angiotensin system may mediate some of the wide ranging renal effects of adenosine.