Regulation of sympathetic presynaptic components in rat left ventricle during ligation of abdominal aorta

Abstract

To assess the effects of long-term pressure overload on sympathetic presynaptic components in the left ventricle, young adult male rats were subjected to surgical constriction of the suprarenal abdominal aorta. At 4 and 8 wk postsurgery, but not at 1 wk, left ventricular sympathetic activity, measured by the net fractional norepinephrine (NE) decrease after alpha-methyl-p-tyrosine methyl ester administration, was elevated in the aortic-banded rats. However, left ventricular NE was reduced only at 8 wk. Scatchard analysis of saturation binding of [3H]nisoxetine, a specific ligand for NE uptake sites, determined that left ventricular NE transporter sites were also reduced at 8 wk, suggesting a relationship between a reduced number of uptake sites and loss of NE stores. In contrast, aortic constriction did not reduce neuropeptide Y (NPY), tyrosine hydroxylase, dopamine beta-hydroxylase, nervegrowth factor, and low-affinity nerve growth factor receptors at any time point. Thus long-term pressure overload can cause a selective reduction in ventricular NE stores without a reduction in NPY, a colocalized sympathetic neurotransmitter.

Renin-angiotensin system and sympathetic nervous system in cardiac pressure-overload hypertrophy

“…In the rat aortic constriction model of cardiac pressure overload, LV norepinephrine (NE) content was decreased within 7-14 days (14,15,39). Reductions in cardiac NE content were generally associated with elevations in catecholamine turnover in the heart, supporting enhanced cardiac sympathetic neurotransmission (14,15,33,39). Increases in cardiac sympathetic neurotransmission have been suggested to contribute to the development of hypertrophy and alterations in cardiac adrenergic receptor function.…”

Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload

“…Direct demonstration of elevated cardiac interstitial NE has also been documented in failing myocardium (12). Increases in interstitial NE in the heart are most likely the result of an increase in cardiac NE release and a decrease in neuronal NE uptake (3,37). Understanding the mechanisms that contribute to activation of the sympathetic nervous system is of significance in the pathophysiology of heart failure because results from clinical studies demonstrate that sympathetic activation is associated with increased mortality in heart failure (13,26,49).…”