Modification of cardiovascular response of posterior hypothalamic adenosine A(2) receptor stimulation by adenylate cylase, guanylate cyclase and by K(ATP) channel blockade in anesthetized rats.
Cardiovascular inhibitory effects induced by posterior hypothalamic adenosine A(2) receptors and their modulation by nitric oxide were suggested by our previous report. In this experiment, we examined the modulation of cardiovascular effects of adenosine A(2) receptor stimulation by adenylate cyclase, guanylate cyclase and ATP-sensitive K(+) channel in the posterior hypothalamus. Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague-Dawley rats. Injection of adenosine A(2) receptor agonist 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 5 nmol) produced a dose-dependent decrease of blood pressure and heart rate. Pretreatment with adenosine A(2) receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 nmol) blocked the depressor and bradycardiac effects of CPCA (5 nmol). Pretreatments with adenylate cyclase inhibitor MDL-12330 (10 nmol) and guanylate cyclase inhibitor LY-83583 (5 nmol) attenuated the depressor and bradycardiac effects of CPCA (5 nmol). In addition, pretreatment with ATP-sensitive K(+) channel blocker glipizide (20 nmol) attenuated the depressor and bradycardiac responses of CPCA (5 nmol). These results suggest that posterior hypothalamic adenosine A(2) receptors play an inhibitory role in the central cardiovascular regulation and that both adenylate cyclase and guanylate cyclase mediate the depressor and bradycardiac actions of adenosine A(2) receptors. Also, ATP-sensitive K(+) channel mediates the posterior hypothalamic cardiovascular regulations of adenosine A(2) receptors.
Kang
Min Jeong
MJ
Department of Pharmacology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Ku, Seoul 133-791, South Korea.
Park
Moon Seung
MS
Shin
In Chul
IC
Koh
Hyun Chul
HC
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C024311:N-cyclopropyl adenosine-5'-carboxamide; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000241:Adenosine