Effects of adenosine receptor subtype A1 on ventricular and renal function.

The adenosine subtype 1 (A 1 ) receptor, which may influence cardiac function and modulate renal function, may have particular relevance in congestive heart failure (CHF). However, the effects of A 1 receptor inhibition in the setting of CHF are poorly defined. Systemic hemodynamics and indices of renal 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 μg of BG9719 (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 left ventricular peak pressure increased following A 1 blockade in the CHF group, consistent with an adenosine inhibitory effect. However, cardiac output and global measures of vascular resistance did not significantly change following A 1 blockade. Urine output increased twofold and sodium clearance increased threefold following At blockade (p < 0.05). Creatinine clearance 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 effects on cardiac function. These unique results suggest that renal A 1 receptor activation may contribute to the reduced renal function associated with CHF.