Microinjection of alpha-calcitonin gene-related peptide into the hypothalamus activates sympathetic outflow in rats.

Effect of rat alpha-calcitonin gene-related peptide (alpha-CGRP) microinjected into various hypothalamic nuclei on plasma levels of catecholamines and arterial blood pressure were investigated in urethane-anesthetized rats. alpha-CGRP (0.05 and 0.25 nmol) microinjected into the hypothalamic paraventricular nucleus (PVN) increased the plasma level of noradrenaline (NA), but not that of adrenaline (AD), in a dose-dependent manner. A similar increase in plasma level of NA was also observed by alpha-CGRP (0.05 nmol) microinjected into the preoptic area (POA), anterior hypothalamus (AH), dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). A significant increase in arterial blood pressure was observed by microinjection of alpha-CGRP (0.05 nmol) into the PVN, POA, AH and DMH, and the most prominent increase was caused by its microinjection into the PVN. Microinjection of the same dose of this peptide into the VMH, lateral hypothalamic area and posterior hypothalamus was without effect. The increase in plasma level of NA induced by alpha-CGRP (0.05 nmol) into the PVN was not affected by bilateral adrenalectomy. Electrical stimulation of the PVN elicited increases in plasma levels of both NA and AD. This increase in NA was abolished by chemical sympathectomy with 6-hydroxydopamine (50 mg/kg, i.v., 3 days before experiments). These results suggest that activation of the PVN by electrical stimulation elicits both sympathetic and adrenomedullary outflow. alpha-CGRP microinjected into the PVN selectively activates the sympathetic outflow.