Anandamide content and interaction of endocannabinoid/GABA modulatory effects in the NTS on baroreflex-evoked sympathoinhibition

Autor: Sachin Patel, Francis A. Hopp, Jeanne L. Seagard, Caron Dean, Cecilia J. Hillard, William T. Schmeling, David J. Rademacher
Rok vydání: 2004
Předmět:
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 286:H992-H1000
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.00870.2003
Popis: Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure (BP). The presence of cannabinoid CB1 receptors on fibers in the nucleus tractus solitarius (NTS) suggests that some presynaptic modulation of transmitter release could occur in this region, which receives direct afferent projections from arterial baroreceptors and cardiac mechanoreceptors. This study, therefore, was performed to determine the mechanism(s) of effects of microinjection of an endocannabinoid, arachidonylethanolamide (anandamide, AEA), into the NTS on baroreflex sympathetic nerve responses produced by phenylephrine-induced pressure changes in anesthetized rats. AEA prolonged reflex inhibition of renal sympathetic nerve activity (RSNA), suggesting an increase in baroreflex sensitivity. This effect of AEA was blocked by prior microinjection of SR-141716 to block cannabinoid CB1 receptors. To determine whether this baroreflex enhancement by AEA involved a GABAA mechanism, the baroreflex response to AEA was tested after prior blockade of postsynaptic GABAA receptors by bicuculline, which would eliminate any effects due to modulation of GABA activity. After bicuculline, which alone prolonged the baroreflex inhibition of RSNA, AEA shortened the duration of RSNA inhibition, suggesting a possible presynaptic inhibition of glutamate release previously obscured by a more dominant GABAA effect. To support a possible physiological role for AEA, AEA concentration in the NTS was measured after a phenylephrine-induced increase in BP. AEA content in the NTS was increased significantly over that in normotensive animals. These results support the hypothesis that AEA content is increased by brief periods of hypertension and suggest that AEA can modulate the baroreflex through activation of CB1 receptors within the NTS, possibly modulating effectiveness of GABA and/or glutamate neurotransmission.
Databáze: OpenAIRE