Abstract P189: Angiotensin II - Endocannabinoid Interactions in the Nucleus of the Solitary Tract are Important for Regulation of Baroreflex Control of Heart Rate

Abstract

Hypertension resulting from elevated brain angiotensin (Ang) II is associated with impaired functioning of neural reflexes regulating sympathetic and parasympathetic outflow. Restoration of normal baroreflex sensitivity (BRS) for control of heart rate (HR) is achieved in a rat model of Ang II - dependent hypertension [ (mRen2)27 transgenic rats ] by local injection of the cannabinoid CB 1 receptor antagonist rimonabant (SR141716A), a CB 1 receptor antagonist, into the solitary tract nucleus (NTS) of anesthetized rats or by chronic oral rimonabant treatment, which has central and peripheral sites of action. Together with elevated brain dorsal medullary tissue concentrations of 2-arachidonylglycerol present in the (mRen2)27 rats, these findings are consistent with an activated endocannabinoid system contributing to the impaired BRS in these animals. To further explore acute interactions between Ang II - mediated suppression of BRS and the endocannabinoids, Ang II was injected into NTS of anesthetized Sprague-Dawley rats 10 minutes following NTS injection of rimonabant or aCSF (120 nL, bilaterally). In the presence of aCSF, Ang II reduced BRS by ~50% (In msec/mm Hg: 1.14 ± 0.14 before versus 0.53 ± 0.16; n = 7, p < 0.008); this effect was abolished in the presence of rimonabant (In msec/mm Hg: 0.92 ± 0.16 before versus 0.86 ± 0.21; n = 4, p = 0.8). There was no difference in mean arterial pressure or heart rate before or after Ang II treatment in either aCSF or rimonabant groups. Thus, the data support the interpretation that Ang II - mediated attenuation of BRS for control of HR involves release of endocannabinoids. Others report that the pressor actions following acute local injections of Ang II into the hypothalamic paraventricular nucleus are prevented by blockade of CB 1 receptors. We conclude that functional interactions between these two systems occur at multiple brain sites relevant to blood pressure control mechanisms and together the findings support a role for elevated brain endocannabinoids as contributors to the altered reflexes characteristic of Ang II - dependent hypertension. Support: HL-51952, DA-024863 and DA-03690, the Hypertension & Vascular Research Center, Farley[[Unable to Display Character: ‐]]Hudson Foundation