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 enzymes: adenyl 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 <0.001). However, phosphodiesterase activity was unchanged. These findings suggest that there is a double biochemical defect in the adrenergic support to the failing heart. In addition to the known reduction of myocardial catecholamines, there appears to be diminished capacity for synthesis of cyclic-AMP, an important mediator of catecholamine action.
- Received October 29, 1968.
- © 1969 American Heart Association, Inc.