Chemical stimulation of the locus coeruleus: inhibitory effects on hemodynamics and renal sympathetic nerve activity

Abstract

We examined the role of the locus coeruleus (LC) in the regulation of the hemodynamics and sympathetic nerve activity in anesthetized rats. Unilateral microinjection into the LC of the excitatory amino acid, l-glutamate (Glu), elicited dose-dependent decreases in arterial pressure (AP) and heart rate (HR). The bradycardic response was partially attenuated after intravenous injection of atropine sulfate, but the greater part of this response still remained. Interruption of the ascending projections of the LC by midbrain of transection did not affect the depressor and bradycardic responses elicited by chemical stimulation. The renal sympathetic nerve activity showed transient but strong inhibition with this stimulation. Cardiac output was measured using an electromagnetic flowmeter implanted in the ascending aorta. The stroke volume and total peripheral resistance (TPR) were calculated. Microinjection of Glu elicited a significant decrease in TPR and slight decreases in cardiac output and stroke volume. Microinjection of the inhibitory amino acid, γ-aminobutyric acid (GABA), or theα 2-adrenergic agonist, clonidine, exerted no effect on AP and HR. The present results therefore suggest that: (1) the LC neurons have an inhibitory influence on the sympathetic nervous system, and stimulation of these neurons can elicit depressor and bradycardic responses; (2) the depressor response was produced predominantly as a result of a decrease in vascular resistance, rather than a decrease in cardiac output; (3) these inhibitory responses may be provided not via the ascending projections of the LC; and (4) the LC neurons do not have a tonic influence on the cardiovascular system.