Abstract
The present study was designed to assess the role of spinal adenosine $A_2$ receptor in the regulation of cardiovascular functions such as mean arterial pressure (MAP) and heart rate (HR) in male Sprague-Dawley rats. Rats (250~300 g) were anesthetized with urethane and paralyzed with d-tubocurarine and artificially ventilated. blood pressure and HR were continuously monitored via a femoral catheter connected to a pressure transducer and a polygraph. Drugs were administered intrathecally using injection cannula through guide cannula which was inserted inthrathecally at lower thoracic level through a puncture of an atlantooccipital mombrane. Intrathecal injection of an adenosine $A_2$ receptor agonist, 5'-(N-cyclopropyl)-carboxamaidoadenosine (CPCA; 1, 2 and 3 nmol, respectively), produced a dose-dependent decrease in MAP and HR. Pretreatment with $N^{G}$-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or 10 nmol of MDL-12,330, an adenylate cyclase inhibitor blocked significantly the depressor and bradycardic effect of 2 nmol of CPCA. But, Pretreatment with 3 nmol of bicuculline, gamma-aminobutyric acid A (GAB $A_{A}$) receptor antagonist, or 50 nmol of 5-aminovaleric acid, GAB $A_{B}$ receptor antagonist did not inhibit the depressor and bradycardic effect of 2 nmol of CPCA. These results indicate that adenosine $A_2$ receptor in the spinal cord plays an inhibitory role in the regulation of cardiovascular function and that the depressor and bradycardic action of adonosine $A_2$ receptor are mediated via the synthesis of nitric oxide and the activation of adenylate cyclase in the spinal cord of rats.s.s.s.
