Lee Chang Beom, Koh Hyun Chul
Department of Internal Medicine, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Ku, Seoul 133-791, Republic of Korea.
Auton Neurosci. 2009 Mar 12;146(1-2):70-5. doi: 10.1016/j.autneu.2008.11.015. Epub 2009 Jan 12.
In this experiment, we examined the influence of the posterior hypothalamic adenosine A(2A) 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 A(2A) receptor agonist, elicited a decrease of arterial BP and HR, while injection of 8-(3-Chlorostyryl)caffeine (CSC; 10 nmol), an adenosine A(2A) receptor antagonist, blocked the depressor and bradycardiac effects of CGS (20 nmol). To examine the mechanisms of cardiovascular regulation of adenosine A(2A) 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 A(2A) 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 A(2A) 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 A(2A) receptors. Furthermore, ATP-sensitive K+ channels mediate the posterior hypothalamic cardiovascular regulation of adenosine A(2A) receptors.
在本实验中，我们研究了下丘脑后部腺苷A(2A)受体对血压（BP）和心率（HR）的中枢心血管调节的影响。在麻醉、人工通气的雄性Sprague-Dawley大鼠中进行下丘脑后部药物注射。注射腺苷A(2A)受体激动剂CGS-21680HCl（CGS；20 nmol）可引起动脉血压和心率下降，而注射腺苷A(2A)受体拮抗剂8-(3-氯苯乙烯基)咖啡因（CSC；10 nmol）可阻断CGS（20 nmol）的降压和减慢心率作用。为了研究下丘脑后部腺苷A(2A)受体的心血管调节机制，我们将腺苷酸环化酶和鸟苷酸环化酶抑制剂应用于下丘脑后部。用腺苷酸环化酶抑制剂MDL-12,330（MDL；10 nmol）预处理可减弱CGS的降压和减慢心率作用。然而，用可溶性鸟苷酸环化酶抑制剂LY-83,583（LY；5 nmol）预处理并未改变CGS的作用。此外，我们研究了通过下丘脑后部ATP敏感性钾通道对腺苷A(2A)受体心血管作用的调节。下丘脑后部给予格列吡嗪（20 nmol）可显著减弱CGS引起的心血管降压作用。这些结果表明，下丘脑后部的腺苷A(2A)受体在中枢心血管调节中起抑制作用，腺苷酸环化酶而非鸟苷酸环化酶介导腺苷A(2A)受体的降压和减慢心率作用。此外，ATP敏感性钾通道介导下丘脑后部腺苷A(2A)受体的心血管调节。
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