Enhanced CB1 Cannabinoid Receptor Tone Contributes to Impaired Baroreflex Sensitivity in Hypertensive (mRen2)27 Transgenic Rats

Abstract

We demonstrated that activation of CB1 cannabinoid receptors within the solitary tract nucleus (NTS) of the brainstem via bilateral microinjection of the CB1 agonist CP55,940 modulates baroreflex sensitivity (BRS) for control of heart rate, an index of vagus nerve function, in a dose‐related biphasic manner. The CB1‐selective antagonist SR141716 (36 pmol) prevented or reversed these changes, and there was no effect of the antagonist alone. We now determine the effects of CB1 receptor blockade in (mRen2)27 (Ren2) rats, a model of angiotensin (Ang) II‐dependent hypertension with impaired baseline BRS. Unlike in Sprague‐Dawley (SD) rats, SR141716 dose‐dependently improved BRS when microinjected into the NTS of Ren2 rats. Microinjection of 0.36 pmol SR141716 (n = 5) increased BRS by 59% (p < 0.001), while 36 pmol SR141716 (n = 5) increased BRS by 124% (p < 0.001), to a level similar to baseline BRS of SD rats. There was no change in BRS by 1.2 pmol CP55,940 (n = 3) in Ren2 rats. Immunoblots revealed a trend for higher CB1 expression in brainstem of the Ren2 strain compared to SD rats. Thus, elevated endocannabinoid actions in the NTS contribute to impaired BRS in Ang II‐dependent hypertension. It is not yet known whether this results from elevated receptors or endogenous levels of the cannabinoids, but CB1 receptor blockade may positively influence BRS in the context of hypertension. Supported by P01‐HL051952 and R01‐DA03690.