Autonomic control of cardiac C-AMP.

Abstract

Although catecholamines are known to increase cyclic adenosine 3'5'-monophosphate (C-AMP) in heart muscle, the relations of adrenergic and cholinergic mechanisms to inotropy and myocardial C-AMP levels and adenyl cyclase have not been defined. Accordingly, atrial and ventricular muscle preparations were studied in a myograph with a tension recorder. Adenyl cyclase, phosphodiesterase, and C-AMP were measured by chromatographic and isotopic methods. In atrial preparations, norepinephrine (10 -5 M ) increased tension by 80±10% (mean± SE ), adenyl cyclase by 40±10% and C-AMP by 75±12%, while carbamylcholine chloride (10 -4 M ) reduced tension by 65±10%, adenyl cyclase by 30±12% and C-AMP by 50±14%. The effects of carbamylcholine chloride on tension, adenyl cyclase, and C-AMP were blocked by atropine 10 -5 M . In paced ventricular (papillary) muscles, norepinephrine (10 -5 M ) increased tension by 70±10%, adenyl cyclase by 50±11% and CAMP by 90±17%. In contrast, carbamylcholine chloride (10 -5 M ) reduced tension by only 7±5%, adenyl cyclase by 12±8%, and C-AMP by 10±7%. These results demonstrate parallel changes in tension, adenyl cyclase, and C-AMP in atrium and ventricle. The failure of ventricular muscle to respond to carbamylcholine is mirrored by the adenyl cyclase system and C-AMP. Furthermore, the cholinergically mediated tension and adenyl cyclase changes in atria were specifically blocked by atropine. Thus these results relate the different effects of cholinergic agents on atrium and ventricle to adenyl cyclase and C-AMP, and suggest specific receptor localization in these two types of myocardia.