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

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(ω)-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 (2mg/Kg); the nonselective β-adrenergic receptor antagonist propranolol (2mg/Kg); the β1-adrenergic receptor selective antagonist atenolol (1mg/kg). However, pretreatment with the selective α1-adrenergic receptor antagonist prazosin (0,5mg/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.

• Authors: Cibele O Santini, Aline Fassini, América A Scopinho, Cristiane Busnardo, Fernando M A Corrêa, Leonardo B M Resstel
• Journal: Autonomic neuroscience : basic & clinical (Auton Neurosci) Vol. 177 Issue 2 Pg. 244-52 (Oct 2013) ISSN: 1872-7484 [Electronic] Netherlands
• PMID: 23735844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Receptors, N-Methyl-D-Aspartate
• Nitric Oxide
• Glutamic Acid
• Guanylate Cyclase

Topics

• Animals
• Blood Pressure (drug effects, physiology)
• Enzyme Inhibitors (administration & dosage)
• Glutamic Acid (administration & dosage)
• Guanylate Cyclase (antagonists & inhibitors, metabolism)
• Heart Rate (drug effects, physiology)
• Hippocampus (drug effects, metabolism)
• Male
• Microinjections (methods)
• Nitric Oxide (antagonists & inhibitors, metabolism)
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (agonists, antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects, physiology)