Sympathetic changes during development of cardiac hypertrophy in aortic-constricted rats

Abstract

Cardiac hypertrophy is frequently associated with sympathetic changes that include increased myocardial norepinephrine turnover, depleted myocardial norepinephrine stores, decreased myocardial responses to sympathetic nerve stimulation, and elevated plasma catecholamines. To better understand these events mechanistically, the time course of each was assessed in rat hearts subjected to aortic constriction-induced pressure overload. There was no evidence of increased left ventricular norepinephrine turnover in abdominal aortic-constricted rats, when compared with sham-constricted animals, during the first 3 days postoperatively. Moreover, their turnover rate constants tended to be lower during this period, then increased significantly by day 7. Plasma catecholamines were increased and left ventricular norepinephrine stores were decreased only on day 7. Heart rate responses to maximal sympathetic nerve stimulation were significantly reduced on the third postoperative day. Thus the decrease in norepinephrine stores coincided with changes in left ventricular norepinephrine turnover and plasma catecholamines, whereas the reduction in heart rate responses did not. This pattern suggests an initial reflex decrease in myocardial sympathetic tone, followed by baroreceptor resetting, with an eventual increase in general sympathetic outflow. The period of increasing catecholamine stimulation occurred after a relative left ventricular hypertrophy had developed but before a significant increase in absolute left ventricular mass. Thus catecholamines may still importantly contribute to the hypertrophy seen in this model.