Atrial natriuretic factor reduces cell coupling in the failing heart, an effect mediated by cyclic GMP.
The influence of the atrial natriuretic factor (ANF) on heart-cell communication was investigated in cell pairs isolated from the ventricle of cardiomyopathic hamsters (BIO TO-2; 11 months old), and the results were compared with controls (F1B) of same age. The results indicated that ANF (10(-8) M) added to the bath caused a decline in junctional conductance (gj) of 48 +/- 2% (n = 15) within 90 s. The effect of ANF was suppressed by HS-142-1, a specific antagonist of guanylyl cyclase ANF receptor. Moreover, the decline in gj elicited by ANF was related to the synthesis of cyclic guanosine monophosphate (cGMP). Indeed, dibutyryl-cGMP (10(-4) M) decreased gj by 80 +/- 3.5% (n = 15) within 90 s, and zaprinast, a selective inhibitor of cGMP phosphodiesterase, enhanced the effect of ANF on gj. The possible relationship between ischemia, ANF release, and impairment of cell coupling is discussed.
De Mello
W C
WC
Department of Pharmacology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan 00936-5067, USA.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D009202:Cardiomyopathies / Q000235:genetics / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects*; D006224:Cricetinae; D006152:Cyclic GMP / Q000502:physiology*; D004594:Electrophysiology; D017629:Gap Junctions / Q000187:drug effects; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors
D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D003994:Bucladesine; D009320:Atrial Natriuretic Factor; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D017461:Receptors, Atrial Natriuretic Factor; C011145:zaprinast; D006152:Cyclic GMP