The ventral hippocampus NMDA receptor/nitric oxide/guanylate cyclase pathway modulates cardiovascular responses in rats

Author(s)

Santini, Cibele O. ^[1] ; Fassini, Aline ^[1] ; Scopinho, America A. ^[1] ; Busnardo, Cristiane ^[1] ; Correa, Fernando M. A. ^[1] ; Resstel, Leonardo B. M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Sao Paulo - Brazil

• Document type: Journal article
• Source: AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL; v. 177, n. 2, p. 244-252, OCT 2013.
• Web of Science Citations: 9

Abstract

The hippocampus is a limbic structure that is involved in the expression of defensive reactions and autonomic changes in rats. The injection of L-glutamate (L-glu) into the ventral hippocampus (VH) decreases blood pressure and heart rate in anesthetized rats. Activation of NMDA receptors in the VH increases the production of nitric oxide (NO), leading to guanylate cyclase activation. The hypothesis of the present study was that a local NMDA receptor-NO-guanylate cyclase interaction mediates the cardiovascular effects of microinjection of L-glu into the VH. Microinjection of increasing doses of L-glu (30, 60 and 200 nmol/200 nL) into the VH of conscious rats caused dose-related pressor and tachycardiac responses. The cardiovascular effects of L-glu were abolished by local pretreatment with: the glutamate receptor antagonist AP-7 (0.4 nmol); the selective neuronal NO synthase (nNOS) inhibitor N-omega-Propyl-L-arginine (0.04 nmol); the NO scavenger C-PTIO (2 nmol) or the guanylate cyclase inhibitor 1H-{[}1,2,4] oxadiazolol {[}4,3-a]quinoxalin-1-one (2 nmol). Moreover, these cardiovascular responses were blocked by intravenous pretreatment with: the ganglionic blocker mecamylamine (2 mg/Kg); the nonselective beta-adrenergic receptor antagonist propranolol (2 mg/Kg); the beta 1-adrenergic receptor selective antagonist atenolol (1 mg/kg). However, pretreatment with the selective alpha 1-adrenergic receptor antagonist prazosin (0,5 mg/kg) caused only a small reduction in the pressor response, without affecting the L-glu evoked tachycardia. In conclusion, our results suggest that cardiovascular responses caused by L-glu microinjection into the VH are mediated by NMDA glutamate receptors and involve local nNOS and guanylate cyclase activation. Moreover, these cardiovascular responses are mainly mediated by cardiac sympathetic nervous system activation, with a small involvement of the vascular sympathetic nervous system. (C) 2013 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 11/13626-0 - Possible MECHANISMS INVOLVED IN PERIPHERAL CARDIOVASCULAR RESPONSES EVOKED BY THE ACTIVATION OF VENTRAL HIPPOCAMPUS NMDA RECEPTORS OF UNAESTHETIZED RATS
• Grantee: Cibele Santini de Oliveira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 09/05308-8 - Role of the hypothalamus paraventricular nucleus on cardiovascular and neuroendocrine responses observed during acute restraint stress in rats
• Grantee: Cristiane Busnardo Santiago
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/07332-3 - Possible role of dorsal hippocampus on behaviour and autonomic responses during defensive responses: involvement of NMDA receptor/nitric oxide and endocanabinoid
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants