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KMID : 0606920060140020119
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Biomolecules & Therapeutics
2006 Volume.14 No. 2 p.119 ~ p.124
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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
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Shin In-Chul
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Abstract
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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), 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 A1 receptor agonist, N6-cyclohexyladenosine (CHA; 1, 5 and 10nmol) produced dose dependent decreased of BP and HR and it was attenuated by pretreatment of 50 nmol of 8-cyclopentyl-1,3-dimethylxanthine, a specific adenosine A1 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. Pre- treatment 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 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 and potassium channel.
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KEYWORD
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adenosine A1 receptor, spinal cord, N6-cyclohexyladenosine, blood pressure, heart rate, cAMP, cGMP, ATP-sensitive potassium channel
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