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 inhibition of receptor-mediated cyclic AMP-dependent relaxation in isolated pulmonary arteries (PA). Since ANF is known to be negatively coupled to adenylate cyclase, we studied cyclic AMP-mediated relaxation to isoprenaline (Iso) and arachidonic acid (AA) in PA from control dogs (C), dogs with pacing-induced CHF (CHF) and dogs with bilateral atrial appendectomy and CHF (ATR APP+CHF). 2. In CHF, plasma ANF levels increased 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, however, did not influence myocardial dysfunction in CHF. 3. The relaxation of 49 +/- 5% to 1 microM 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 group (P = NS vs C). Relaxation responses to 10 microM AA were as follows: 77 +/- 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, did not affect responses to cyclic GMP-mediated relaxing agents in PA. 4. These data indicate that the myocardial performance in CHF is not influenced by plasma ANF levels. However, altered cyclic AMP-mediated relaxation in PA during CHF is, in part, modulated by circulating ANF levels.
Mathew
R
R
Department of Paediatrics, New York Medical College, Valhalla 10595, USA.
Omar
H A
HA
Fayngersh
R
R
Shen
W
W
Wang
J
J
Gewitz
M H
MH
Hintze
T H
TH
Wolin
M S
MS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000188:drug therapy*; D009126:Muscle Relaxation / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*
D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D000109:Acetylcholine; D001920:Bradykinin