Effects of selective A1 receptor blockade on glomerular hemodynamics: involvement of renin-angiotensin system.

We examined the renal effects of a specific adenosine A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 micrograms.kg-1.min-1 iv). Since adenosine is a potent inhibitor of renin release, additional experiments were performed with an angiotensin AT1-receptor antagonist (losartan, 10 mg/kg i.v.). DP CPX alone induced a significant (P < 0.05) decrease in afferent arteriolar resistance (RA, 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 (Kf) 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 RA and delta P. Also, DPCPX increased Kf (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.