Involvement of NO and K-ATP Channel in Adenosine A(2B) Receptors Induced Cardiovascular Regulation in the Posterior Hypothalamus of Rats

Abstract

Previous reports have suggested that the posterior hypothalamic adenosine A, receptors may play a role in central cardiovascular regulation. In this study, we examined the influence of posterior hypothalamic adenosine A(2B) receptors oil the regulation of blood pressure and heart rate. Drugs were injected into the posterior hypothalamus of anesthetized, artificially ventilated, male Sprague-Dawley rats. Four nanomoles of 5'-N-ethylcarboxamidoadenosine (NECA), ail adenosine A(2A) receptor agonist, decreased arterial blood pressure and heart rate, whereas 5 nmol of alloxazine, ail adenosine AM receptor antagonist, blocked the depressor and bradycardiac effects of 4 nmol NECA. We examined the role of nitric oxide (NO) and K+ channels on cardiovascular regulation by adenosine A(2B) receptors in the posterior hypothalamus. Pretreatment with 40 nmol of N-G-nitro-l-arginine methyl ester, a NO synthase inhibitor, significantly attenuated the effects of NECA, and 10 nmol of sodium nitroprusside, a NO releaser, strengthened the action of drug. In addition, posterior hypothalamic administration of 20 nmol of glipizide, an K-ATP blocker, blocked the cardiovascular depression elicited by NECA. These results suggest that NO mediates cardiovascular regulation by activation of A(2B) receptors in the posterior hypothalamus. Additionally, ATP-sensitive K+ channels modulate the action of adenosine A,B receptors.