title: Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs.
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 CB(1) 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 CB(1) 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 CB(1) 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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Rademacher
authors.forename: Sachin
authors.initials: S
authors.lastname: Patel
authors.forename: Francis A
authors.initials: FA
authors.lastname: Hopp
authors.forename: Caron
authors.initials: C
authors.lastname: Dean
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.forename: Jeanne L
authors.initials: JL
authors.lastname: Seagard
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D048588:Benzoxazines; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D063385:Cannabinoid Receptor Modulators; D004285:Dogs; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000502:physiology; D000077285:Rimonabant; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant