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Modulation of N-methyl-d-aspartate receptors in isolated rat heart

Can J Physiol Pharmacol. 2017 Nov;95(11):1327-1334. doi: 10.1139/cjpp-2017-0056. Epub 2017 Jul 30.

Abstract

Considering the limited data on the role of NMDA-Rs in the cardiovascular system, the aim of the present study was to examine the effects of NMDA and DL-Hcy TLHC, alone and in combination with glycine, memantine, and ifenprodil, in the isolated rat heart. The hearts of Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure. The experimental protocol for all experimental groups included the stabilization period, application of estimated substance for 5 min, followed by a washout period of 10 min. Using a sensor placed in the left ventricle, we registered the following parameters of myocardial function: dp/dtmax, dp/dtmin, SLVP, DVLP, HR; CF was measured using flowmetry). We estimated the following oxidative stress biomarkers in the coronary venous effluent using spectrophotometry: TBARS, NO2-, O2-, and H2O2. NMDA alone did not induce any change in any of the observed parameters, while DL-Hcy TLHC alone, as well as a combined application of NMDA and DL-Hcy TLHC with glycine, induced a reduction of most cardiodynamic parameters. Memantine and ifenprodil induced a reduction of cardiodynamic parameters and CF, as well as some oxidative stress biomarkers.

Keywords: N-methyl-d-aspartate receptors; cardiodynamics; cardiodynamie; cœur isolé de rat; homocysteine; homocystéine; ifenprodil; isolated rat heart; memantine; mémantine; oxidative stress; récepteurs du N-méthyl-d-aspartate; stress oxydatif.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Heart / drug effects
  • Homocysteine / analogs & derivatives
  • Homocysteine / pharmacology
  • Male
  • Myocardium / metabolism*
  • N-Methylaspartate / pharmacology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • Biomarkers
  • Receptors, N-Methyl-D-Aspartate
  • Homocysteine
  • N-Methylaspartate
  • homocysteine thiolactone