Cardiovascular effects produced by L-glutamate stimulation of the lateral hypothalamic area

Abstract

L-Glutamate microinjections into the tuberal region of the lateral hypothalamic area (LHAt) caused a fall in blood pressure and heart rate in pentobarbital-anesthetized rats. The bradycardia was mediated by both beta-adrenergic and muscarinic mechanisms as demonstrated with pharmacological blockade. The hypotension was due to a decrease in cardiac output, not a decrease in total peripheral resistance. In addition, there was a reduction in coronary blood flow. If heart rate was held constant by pharmacological blockade or by electrical cardiac pacing, L-glutamate stimulation of the LHAt still caused a fall in blood pressure. When the electrically paced model was used, this hypotension was due to a fall in cardiac output. In contrast, with the pharmacological blockade of the heart, the hypotension was due to a decrease in the total peripheral resistance. The cardiac output reduction in the paced condition was not mediated solely by either beta-sympathetic or parasympathetic mechanisms as determined by pharmacological blockade. With heart rate held constant by either drugs or pacing, LHAt stimulation did not alter regional blood flow or resistance in any vascular bed, including the coronary circulation. We conclude that L-glutamate stimulation of the LHAt lowers the cardiac output and heart rate by both parasympathetic and beta-adrenergic mechanisms and elicits hypotension by lowering cardiac output in the naive and electrically paced model.

Corticotropin-Releasing Factor Induces Differential Behavioral and Cardiovascular Effects after Intracerebroventricular and Lateral Hypothalamic/Perifornical Injections in Rats

“…In search of distinct sites in the LH area for regulation of the cardiovascular system, MAP and HR have been recorded after electrical or chemical stim ulation of distinct sites in the LH area. Based on results obtained after electrical stimulation, the LH area has been divided into a rostral depressor area and a more caudally located pressor area [29], Using chemical stimuli, however, a depressor response and bradycardia have been observed [17,40]. According to studies by Arase et al [2], the LH region is involved in the media tion of sympathoinhibitory activity.…”

“…According to studies by Arase et al [2], the LH region is involved in the media tion of sympathoinhibitory activity. The differential ef fects may be explained by the different methods used, whereby electrical stimulation affects fibers of passage and chemical stimulation results in the excitation of cells intrinsic to the LH region [17,26,29,40]. Besides, many of these studies have been carried out in anesthetized animals so that not only the central action of the anes thetics used may influence the results, but also the ab sence of spontaneous behavior.…”

“…In spite of these controversial data, all studies suggest the existence of a certain site specificity in the LH area for various responses [17,40,50,51]. The demonstration of CRFandCRFbindingsitesin the LH area may link neuroanatomical structures and neurochemical substrates to physiological function.…”

“…Physiological studies have demonstrated the involve ment of the LH area in the regulation of peripheral me tabolism, endocrine activity and cardiovascular control [2,40,50,51]. Neuroanatomical studies have established that the LH projects to the intermediolateral cell column and the vagal preganglionic nuclei [3, 20, 37.…”

“…45, 48], In addition, it projects to other central autonomic sites such as the central gray matter, parabrachial nuclei, and nu cleus of the solitary tract [9,37], All of these areas could potentially affect cardiovascular function either directly or indirectly. Studies using chemical and electrical stimula tion of the LH/perifornical area (PFx) have provided evi dence for its role in cardiovascular regulation [ 17,40,50]. The often controversial results regarding the magnitude and direction of effects are due to a site specificity and difference in methodology [17].…”