Effects of adenosine receptor subtype A(1) on ventricular and renal function

The adenosine subtype 1 (A(1)) receptor, which may influence cardiac functi on and modulate renal function, may have particular relevance in congestive heart failure (CHF). However, the effects of A, receptor inhibition in the setting of CHF are poorly defined. Systemic hemodynamics and indices of re nal function were measured in pigs with pacing-induced CHF at 240 bpm for 3 weeks (n = 10) before and after A(1) receptor blockade with 100 mug of BG9 719 (1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthene) or in CHF pigs after infusion of vehicle only (n = 10). Heart rate, mean aortic pressure, and le ft ventricular peak pressure increased following A(1) blockade in the CHF g roup, consistent with an adenosine inhibitory effect. However, cardiac outp ut and global measures of vascular resistance did not significantly change following A(1) blockade. Urine output increased twofold and sodium clearanc e increased threefold following A(1) blockade (p < 0.05). Creatinine cleara nce increased following A(1) blockade (127 +/- 17 vs. 62 +/- 7 ml/min, p < 0.05). Selective A(1) receptor blockade improved glomerular filtration rate and induced a natriuresis and diuresis in a model of CHF without adverse e ffects on cardiac function. These unique results suggest that renal A(1) re ceptor activation may contribute to the reduced renal function associated w ith CHF.