Depressed Adenyl Cyclase Activity in the Failing Guinea Pig Heart

There is considerable evidence that several effects of catecholamines on beta receptors, including the positive inotropic effect on the heart, are mediated by cyclic-AMP. Myocardial cyclic-AMP concentration depends on the activity of at least two enzymesadenyl cyclase, regulating synthesis, and phosphodiesterase, regulating degradation of the compound. In view of the importance of adrenergic support in maintaining cardiac performance, we examined synthesis and degradation of cyclic-AMP in homogenates of hearts from guinea pigs with congestive heart failure produced by constriction of the ascending aorta and from sham-operated controls. In the experimental group, left ventricular weight, DNA, RNA, and protein content were significantly increased 7 to 12 days following operation, and congestive heart failure developed, manifested by hydrothorax, hepatomegaly, and histologic evidence of pulmonary edema and passive congestion of viscera. Adenyl cyclase activity in homogenates from the experimental group was 36% less than that observed in controls (P