Modification of cardiovascular response of adenosine A1 receptor agonist by cyclic AMP in the spinal cord of the rats.
This study was performed to investigate the influence of the spinal adenosine A1 receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by cyclic AMP (cAMP) or cyclic GMP (cGMP). Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. Injection (i.t.) of adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR. Pretreatment with a cAMP analogue, 8-bromo-cAMP, attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. These results suggest that adenosine A1 receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that this depressor and bradycardiac actions are mediated by cAMP.
Koh
H C
HC
Department of Pharmacology, College of Medicine, Hanyang University, Sungdong-Ku, Seoul, South Korea.
Shin
I C
IC
Hwang
S J
SJ
Paik
D J
DJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*
D058906:Purinergic P1 Receptor Agonists; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; C027513:N(6)-cyclohexyladenosine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000241:Adenosine