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 A(2) receptors were suggested by our previous reports. In this experiment, we examined the influence of the posterior hypothalamic adenosine A(2B) 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 A(2) receptor agonist, showed the decrease of arterial blood pressure and heart rate, and the alloxazine, an adenosine A(2B) receptor antagonist, partially blocked the depressor and bradycardiac effects of CPCA (2 nmol). To examine the role of adenosine A(2B) receptors among the adenosine A(2) subtypes, we applied the 5'-N-Ethylcarboxamidoadenosine (NECA), an adenosine A(2B) 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 A(2B) 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 A(2B) receptors.
Kang
Min Jeong
MJ
Department of Pharmacology, 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 / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001919:Bradycardia / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005415:Flavins / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000502:physiology*; D007097:Imines / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D043683:Receptors, Adenosine A2 / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D005415:Flavins; D007097:Imines; D043704:Receptor, Adenosine A2B; D043683:Receptors, Adenosine A2; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); C008173:isoalloxazine; C024311:N-cyclopropyl adenosine-5'-carboxamide; C014925:RMI 12330A; C041715:6-anilino-5,8-quinolinedione; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000241:Adenosine