zaprinast and Cardiomyopathies

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.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Atrial Natriuretic Factor; Bucladesine; Cardiomyopathies; Cell Communication; Cricetinae; Cyclic GMP; Electrophysiology; Gap Junctions; Heart Failure; Heart Ventricles; Male; Mesocricetus; Phosphodiesterase Inhibitors; Purinones; Receptors, Atrial Natriuretic Factor