Effects of adenosine receptor subtype A1 on ventricular and renal function

The adenosine subtype 1 (A1) receptor, which may influence cardiac function and modulate renal function, may have particular relevance in congestive heart failure (CHF). However, the effects of A1 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 A1 receptor blockade with 100 microg 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 A1 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 A1 blockade. Urine output increased twofold and sodium clearance increased threefold following A1 blockade (p < 0.05). Creatinine clearance increased following A1 blockade (127 +/- 17 vs. 62 +/- 7 ml/min, p < 0.05). Selective A1 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 A1 receptor activation may contribute to the reduced renal function associated with CHF.