MODULATION BY ATRIAL-NATRIURETIC-FACTOR OF RECEPTOR-MEDIATED CYCLIC-AMP-DEPENDENT RESPONSES IN CANINE PULMONARY-ARTERY DURING HEART-FAILURE

1 Pacing-induced congestive heart failure (CHF) in dogs is associated with increased plasma levels of atrial natriuretic factor (ANF) and in hibiton of receptor-mediated cyclic AMP-dependent relaxation in isolat ed pulmonary arteries (PA). Since ANF is known to be negatively couple d to adenylate cyclase, we studied cyclic AMP-mediated relaxation to i soprenaline (Iso) and arachidonic acid (AA) in PA from control dogs (C ), dogs with pacing-induced CHF (CHF) and dogs with bilateral atrial a ppendectomy and CHF (ATR APP + CHF). 2 In CHF, plasma ANF levels incre ased from a baseline of 80 +/- 8 pg ml(-1) to 283 +/- 64 pg ml(-1) (P< 0.05), but the ATR APP + CHF group failed to show this increase (67 +/ - 7 pg ml(-1) vs 94 +/- 15 pg ml(-1), P=NS). Plasma ANF levels, howeve r, did not influence myocardial dysfunction in CHF. 3 The relaxation o f 49 +/- 5% to 1 mu M Iso in C was reduced to 23 +/- 4% in CHF (P<0.05 ), but relaxation of 49 +/- 12% was observed in the ATR APP +/- CHF gr oup (P=NS vs C). Relaxation responses to 10 mu M AA were as follows: 7 7 +/- 5% (C, n=8), 27 +/- 8% (CHF, n=10, P<0.05 vs C), and 93 +/- 5% ( ATR APP + CHF, n=5). The presence of CHF, or the plasma ANF levels, di d not affect responses to cyclic GMP-mediated relaxing agents in PA. 4 These data indicate that the myocardial performance in CHF is not inf luenced by plasma ANF levels. However, altered cyclic AMP-mediated rel axation in PA during CHF is, in part, modulated by circulating ANF lev els.