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.
Department of Pharmacology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan 00936-5067, USA.
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De Mello
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