Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs

David J. Rademacher, Sachin Patel, Francis A. Hopp, Caron Dean, Cecilia J. Hillard*, Jeanne L. Seagard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Baroreceptor afferent fibers synapse in the nucleus tractus solitarius (NTS) of the medulla. Neuronal cannabinoid (CB)1 receptors are expressed in the NTS and central administration of CB1 receptor agonists affect blood pressure (BP) and heart rate. In addition, there is evidence that endocannabinoids are produced in the brain stem. This study examined whether changes in CB1 receptor activity in the NTS modulated the baroreceptor reflex, contributing to changes seen in BP and heart rate. Baroreflexes were evoked in anesthetized dogs by pressure ramp stimulations of the isolated carotid sinus before and after microinjection of CB1 receptor agonist WIN-55212-2 (1.25-1.50 pmol) or antagonist SR-141716 (2.5-3.0 pmol) into cardiovascular regions of the NTS. Microinjection of the SR-141716 did not affect baseline BP or baroreflex sensitivity. However, SR-141716 significantly prolonged the time needed to return to the baseline level of BP after the pressure ramp. Microinjection of WIN-55212-2 had no effect on the baroreflex. These data suggest that endocannabinoids can modulate the excitability of NTS neurons involved in the baroreceptor reflex, leading to modulation of baroreflex regulation.

Original languageEnglish (US)
Pages (from-to)H1570-H1576
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number5 53-5
DOIs
StatePublished - May 1 2003
Externally publishedYes

Keywords

  • Endocannabinoids
  • Glutamate
  • SR-141716
  • Sympathetic outflow
  • WIN-55212-2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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