Effect of neurotransmitter release on myocardial cyclic nucleotides during left ventricular tachycardia.
Myocardial levels of neurotransmitters and cyclic nucleotides during left ventricular tachycardia were explored in anesthetized open-chest dogs subjected to heart rates averaging 36% above control. Tachycardia was produced by implanting stimulating electrodes on the epicardial surface of the left ventricle. Arterial systolic (-40%) and diastolic (-45%) blood pressures, cardiac output (-33%), and rate of left ventricular pressure rise (LVdP/dt; -45%) were significantly decreased during a 6-min period of stimulation. These changes were accompanied by a 3.5-times greater efflux of norepinephrine than control, while cardiac muscle norepinephrine declined 34%. In tachycardia, arterial blood levels of norepinephrine and epinephrine were significantly elevated. The increased release of norepinephrine was associated with a 24% rise in myocardial levels of adenosine 3',5'-monophosphate (cAMP). Indicative of a secretion of acetylcholine from the heart was the resulting increase in myocardial concentration of guanosine 3',5'-monophosphate (cGMP; 100%). Although the rise in cGMP was significantly correlated with the decline in LVdP/dt, blockade of the increase in cGMP with atropine did not reverse the decline LVdP/dt. Despite the elevation of norepinephrine and cAMP and their action in stimulating the contractile state of the heart, depressed cardiac function observed in tachycardia can mainly be attributed to global asynchrony of myocardial contraction.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004285:Dogs; D006439:Hemodynamics; D009206:Myocardium / Q000032:analysis* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis; D009712:Nucleotides, Cyclic / Q000032:analysis*; D013610:Tachycardia / Q000378:metabolism*
D018377:Neurotransmitter Agents; D009712:Nucleotides, Cyclic; D000242:Cyclic AMP; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine