Modification of the cardiovascular response of posterior hypothalamic adenosine A2A receptor stimulation by adenylate cyclase and KATP channel blockade in anesthetized rats

In this experiment, we examined the influence of the posterior hypothalamic adenosine A2A receptors on the 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 CGS-21680HCl (CGS; 20 nmol), an adenosine A2A receptor agonist, elicited a decrease of arterial BP and HR, while injection of 8-(3-Chlorostyryl)caffeine (CSC; 10 nmol), an adenosine A2A receptor antagonist, blocked the depressor and bradycardiac effects of CGS (20 nmol). To examine the mechanisms of cardiovascular regulation of adenosine A2A receptors in the posterior hypothalamus, we applied the adenylate cyclase and guanylate cyclase inhibitors, to the posterior hypothalamus. Pretreatment with MDL-12,330 (MDL; 10 nmol), an adenylate cylase inhibitor, attenuated the depressor and bradycardiac effects of CGS. However, pretreatment with, LY-83,583 (LY; 5 nmol), a soluble guanylate cyclase inhibitor, did not alter the effects of CGS. Additionally, we examined the modification of the cardiovascular effects of adenosine A2A receptors through the ATP-sensitive K+ channel in the posterior hypothalamus. Posterior hypothalamic administration of glipizide (20 nmol) significantly attenuated the cardiovascular depressor actions elicited by CGS. These results suggest that adenosine A2A receptors in the posterior hypothalamus play an inhibitory role in central cardiovascular regulation, and that adenylate cyclase, but not guanylate cyclase, mediates the depressor and bradycardiac actions of adenosine A2A receptors. Furthermore, ATP-sensitive K+ channels mediate the posterior hypothalamic cardiovascular regulation of adenosine A2A receptors.