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Effects of chronic blockade of cannabinoid 1 receptors in the NTS on blood pressure in Sprague Dawley rats
Author(s) -
Hopp Francis A,
Dean Caron,
Hillard Cecilia J,
Seagard Jeanne L
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.624.5
Subject(s) - endocannabinoid system , rimonabant , cannabinoid , blockade , cannabinoid receptor , blood pressure , medicine , endocrinology , microinjection , am251 , gabaergic , baroreflex , antagonist , receptor , chemistry , heart rate
Previously, we have shown that endocannabinoid activation of cannabinoid 1 receptors (CB1Rs) in the nucleus tractus solitarius (NTS) prolongs baroreflex inhibition of renal sympathetic nerve activity (RSNA) via modulation of GABAergic transmission in normotensive Wistar Kyoto (WKY) and Sprague Dawley (SD) rats, but not spontaneously hypertensive rats (SHR). These results suggest that CB1R modulation of GABAergic transmission in SHRs is reduced and could contribute to elevated blood pressure (BP) and sympathetic tone characteristic of this model. This study examined the effects of chronic blockade of CB1Rs, mimicking the decrease in CB1R regulation in SHRs, on BP regulation in SD rats. To block CB1Rs, microinjections of the CB1R antagonist SR141716 (70nl; 10 or 20 micromolar) through indwelling guide cannulae into the barosensitive region of the NTS were performed daily for 7 days in rats instrumented with transmitters for telemetry recording of BP. The higher dose of SR141716 produced a sustained increase in BP by day 3, with only transient increases in BP seen in response to microinjection of low‐dose SR141716. The results suggest that loss of endocannabinoid signaling in the NTS can lead to sustained increases in BP in normotensive rats. VA Medical Research Funds (JLS), American Heart Grant‐in‐Aid 0750010Z (CD), NSF Award IOS 0751613 (CD) and NIDA Award DA09155 (CJH).