Stimulation of brain cannabinoid CB receptors can ameliorate hypertension in spontaneously hypertensive rats.

Excessive activation of the sympatho-adrenomedullary system plays a pathogenic role in triggering and sustaining essential hypertension. We previously reported that, in normotensive rats, intracerebroventricularly (i.c.v.) administered neuropeptides, corticotropin-releasing factor and bombesin induced activation of the sympatho-adrenomedullary system, and that brain cannabinoid CB receptors negatively regulated this activation. In this study, we investigated the effects of brain CB receptor stimulation on blood pressure and the sympatho-adrenomedullary outflow in spontaneously hypertensive rats (SHRs), commonly used animal models of essential hypertension, and in Wistar-Kyoto (WKY) rats, normotensive controls of SHRs. In 18-week-old SHRs and WKY rats under urethane anaesthesia (1.0 g/kg, i.p.), SHRs exhibited significantly higher systolic, mean and diastolic blood pressures and plasma noradrenaline and adrenaline, and a lower heart rate than WKY rats. Single administration of arachidonyl 2'-chloroethylamide (ACEA, CB agonist, 1.4 µmol/animal, i.c.v.) significantly but partially reduced mean and diastolic blood pressures and the plasma level of noradrenaline in SHRs compared to vehicle (N,N-dimethylformamide)-treated SHRs. These ACEA-induced reductions were abolished by central pretreatment with rimonabant (CB antagonist, 300 nmol/animal, i.c.v.), which alone showed no significant effect on blood pressures or plasma noradrenaline and adrenaline levels of SHRs. On the other hand, ACEA had no significant effect on blood pressure or plasma noradrenaline and adrenaline levels in WKY rats. These results suggest that stimulation of brain CB receptors can ameliorate hypertension accompanied by enhanced sympathetic outflow without affecting blood pressure under normotensive conditions.