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Effects of KATP Channel Blocker, cAMP and cGMP on the Cardiovascular Response of Adenosine A1 Agonist in the Spinal Cord of the Rats  

Shin In-Chul (Department of Pharmacology, College of Medicine, Hanyang University)
Publication Information
Biomolecules & Therapeutics / v.14, no.2, 2006 , pp. 119-124 More about this Journal
Abstract
This study was performed to investigate the influence of the spinal adenosine $A_1$ 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), cyclic GMP (cGMP) or potassium channel. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. I.t. injection of adenosine $A_1$ receptor agonist, $N^6$-cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR and it was attenuated by pretreatment of 50 nmol of 8-cyclopentyl-1,3-dimethylxanthine, a specific adenosine $A_1$ receptor antagonist. Pretreatment with a cAMP analogue, 8-bromo-cAMP, also attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. Pretreatment with a ATP-sensitive potassium channel blocker, glipizide (20 nmol) also attenuated the depressor and bradycardiac effects of CHA (10 nmol). These results suggest that adenosine $A_1$ 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 and potassium channel.
Keywords
adenosine $A_1$ receptor; spinal cord; $N^6$-cyclohexyladenosine; blood pressure; heart rate; cAMP; cGMP; ATP-sensitive potassium channel;
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