Involvement of guanylate cyclase in the cardiovascular response induced by adenosine A2B receptor stimulation in the posterior hypothalamus of the anesthetized rats

Cardiovascular inhibitory effects induced by the posterior hypothalamic adenosine A2 receptors were suggested by our previous reports. In this experiment, we examined the influence of the posterior hypothalamic adenosine A2B receptors on central cardiovascular regulation of blood pressure (BP) and heart rate (HR). Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection of 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 2 nmol), an adenosine A2 receptor agonist, showed the decrease of arterial blood pressure and heart rate, and the alloxazine, an adenosine A2B receptor antagonist, partially blocked the depressor and bradycardiac effects of CPCA (2 nmol). To examine the role of adenosine A2B receptors among the adenosine A2 subtypes, we applied the 5′-N-Ethylcarboxamidoadenosine (NECA), an adenosine A2B receptor agonist, to the posterior hypothalamus. Injection of NECA (1, 4 and 8 nmol) produced a dose-dependent decrease of arterial blood pressure and HR. Pretreatment with alloxazine (5 nmol) partially blocked the depressor and bradycardiac effects of NECA (4 nmol). Also, pretreatment with LY-83,583 (5 nmol), a soluble guanylate cyclase inhibitor, attenuated the depressor and bradycardiac effects of NECA (4 nmol). However, pretreatment with MDL-12,330 (10 nmol), an adenylate cyclase inhibitor, did not affect these effects of NECA (4 nmol). These results suggest that adenosine A2B receptor in the posterior hypothalamus plays an inhibitory role in central cardiovascular regulation, and that guanylate cyclase mediates the depressor and bradycardiac actions of adenosine A2B receptors.