NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase

Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1521-7. doi: 10.1152/ajpheart.00236.2003.

Abstract

We sought to test the hypothesis that cardiovascular responses to activation of ionotropic, but not metabotropic, glutamate receptors in the nucleus tractus solitarii (NTS) depend on soluble guanylate cyclase (sGC) and that inhibition of sGC would attenuate baroreflex responses to changes in arterial pressure. In adult male Sprague-Dawley rats anesthetized with chloralose, the ionotropic receptor agonists N-methyl-d-aspartate (NMDA) and dl-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and the metabotropic receptor agonist trans-dl-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were microinjected into the NTS before and after microinjection of sGC inhibitors at the same site. Inhibition of sGC produced significant dose-dependent attenuation of cardiovascular responses to NMDA but did not alter responses produced by injection of AMPA or ACPD. Bilateral inhibition of sGC did not alter arterial pressure, nor did it attenuate baroreflex responses to pharmacologically induced changes in arterial pressure. This study links sGC with NMDA, but not AMPA or metabotropic, receptors in cardiovascular signal transduction through NTS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminoquinolines / pharmacology
  • Animals
  • Baroreflex / drug effects
  • Baroreflex / physiology
  • Biotransformation / physiology
  • Blood Pressure / drug effects
  • Cycloleucine / administration & dosage
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / physiology*
  • In Vitro Techniques
  • Male
  • Microinjections
  • N-Methylaspartate / administration & dosage
  • N-Methylaspartate / pharmacology
  • Nitric Oxide / physiology
  • Oxadiazoles / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Solitary Nucleus / enzymology
  • Solitary Nucleus / metabolism*
  • Stereotaxic Techniques
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / administration & dosage
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
  • Aminoquinolines
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Oxadiazoles
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Nitric Oxide
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • 6-anilino-5,8-quinolinedione
  • Guanylate Cyclase