Cardiac cyclic nucleotides and norepinephrine during neural sympathetic stimulation

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Abstract
The role of the cardiac cyclic nucleotides, cAMP and cGMP and norepinephrine (NE) in cardiac responses to stimulation of the left ansa subclavia were studied in anesthetized open-chest dogs. In 3 groups of dogs undergoing stimulation for 6 min with impulse frequencies of 4, 10 or 20 Hz and 5 V, left ventricular levels of cAMP, cGMP and NE were determined at the end of the stimulation period and compared to control dogs. A significant elevation in cAMP (average 67%) was found at all 3 frequencies. Myocardial NE decreased by an average of 58% from control by the end of the stimulation period, regardless of the stimulation frequency. The rate of left ventricular pressure rise (LV dP/dt) was linearly related to the increase in myocaridal cAMP (P < 0.01) rather than to NE levels found after stimulation. Propranolol administered before ansa subclavia stimulation caused significant decreases in cAMP and LV dP/dt; whereas the muscarinic agonist, carbachol, caused increases in cGMP and NE and a decrease in LV dP/dt accompanied by a nonsignificant decline in cAMP. The elevation in levels of cGMP and NE and the decrease in LV dP/dt to carbachol were blocked with atropine. Results from pretreating dogs with propranolol and carbachol followed by neural sympathetic stimulation indicated the importance of .beta.-adrenergic and muscarinic receptors in modifying cardiac function through the production of the cyclic nucleotides. Sustained cardiac responses during ansa subclavia stimulation at physiological levels could be related to the accelerated synthesis of endogenous cAMP.