Modification of the cardiovascular response of posterior hypothalamic adenosine A(2A) receptor stimulation by adenylate cyclase and KATP channel blockade in anesthetized rats.
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.
Lee
Chang Beom
CB
Department of Internal Medicine, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Ku, Seoul 133-791, Republic of Korea.
Koh
Hyun Chul
HC
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology*; D000634:Aminoquinolines / Q000494:pharmacology; D000769:Anesthesia, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001919:Bradycardia / Q000139:chemically induced / Q000517:prevention & control; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D005913:Glipizide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology; D006339:Heart Rate / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000502:physiology*; D007097:Imines / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors; D008297:Male; D008845:Microinjections; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000502:physiology*
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D000634:Aminoquinolines; D007097:Imines; D054086:KATP Channels; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; C014925:RMI 12330A; C041715:6-anilino-5,8-quinolinedione; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000241:Adenosine; D005913:Glipizide