Modification of cardiovascular response of posterior hypothalamic adenosine A 2 receptor stimulation by adenylate cylase, guanylate cyclase and by K ATP channel blockade in anesthetized rats

Abstract

Cardiovascular inhibitory effects induced by posterior hypothalamic adenosine A 2 receptors and their modulation by nitric oxide were suggested by our previous report. In this experiment, we examined the modulation of cardiovascular effects of adenosine A 2 receptor stimulation by adenylate cyclase, guanylate cyclase and ATP-sensitive K + channel in the posterior hypothalamus. Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection of adenosine A 2 receptor agonist 5′-( N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 5 nmol) produced a dose-dependent decrease of blood pressure and heart rate. Pretreatment with adenosine A 2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 nmol) blocked the depressor and bradycardiac effects of CPCA (5 nmol). Pretreatments with adenylate cyclase inhibitor MDL-12,330 (10 nmol) and guanylate cyclase inhibitor LY-83,583 (5 nmol) attenuated the depressor and bradycardiac effects of CPCA (5 nmol). In addition, pretreatment with ATP-sensitive K + channel blocker glipizide (20 nmol) attenuated the depressor and bradycardiac responses of CPCA (5 nmol). These results suggest that posterior hypothalamic adenosine A 2 receptors play an inhibitory role in the central cardiovascular regulation and that both adenylate cyclase and guanylate cyclase mediate the depressor and bradycardiac actions of adenosine A 2 receptors. Also, ATP-sensitive K + channel mediates the posterior hypothalamic cardiovascular regulations of adenosine A 2 receptors.