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Am J Physiol Heart Circ Physiol 284: H1570-H1576, 2003. First published January 9, 2003; doi:10.1152/ajpheart.00772.2002
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Vol. 284, Issue 5, H1570-H1576, May 2003

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

David J. Rademacher1, Sachin Patel1, Francis A. Hopp2,3, Caron Dean2,3, Cecilia J. Hillard1, and Jeanne L. Seagard2,3

Departments of 1 Pharmacology and Toxicology, and 2 Anesthesiology, Medical College of Wisconsin, Milwaukee 53226-0509; and 3 Zablocki Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295

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.

endocannabinoids; sympathetic outflow; glutamate; SR-141716; WIN-55212-2


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