Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

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Abstract
Summary: . The effects of exogenous guanosine 5′‐triphosphate (GTP) and guanosine on vascular tone and cyclic nucleotide accumulation of noradrenaline‐precontracted endothelium‐intact and endothelium‐denuded rat mesenteric artery rings were compared with the effects of the known purinoceptor agonists adenosine 5′‐triphosphate (ATP) and adenosine. . GTP (10 μm−1 mm) dose‐dependently relaxed endothelium‐intact mesenteric artery rings by producing a rapid initial response followed by sustained relaxation resembling the relaxant response to acetylcholine. GTP also slightly relaxed endothelium‐denuded artery rings. The acetylcholine‐ and GTP‐induced relaxations of endothelium‐intact rings were attenuated by NG‐nitro l‐arginine methyl ester (l‐NAME, 330 μm) which attenuation was reversed with l‐arginine (1 mm). . Guanosine (10 μm−1 mm) relaxed both endothelium‐intact and ‐denuded artery rings in a dose‐dependent manner. The relaxations were more pronounced in endothelium‐intact preparations and were only slightly attenuated by l‐NAME (330 μm). . ATP (1 μm−1 mm) and adenosine (10 μm−1 mm) dose‐dependently relaxed endothelium‐intact and ‐denuded artery rings. The responses were more pronounced in endothelium‐intact vascular preparations. . GTP (100 μm) and guanosine (100 μm) increased guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) accumulation in both endothelium‐intact and ‐denuded artery rings corresponding to the relaxations observed. The concentrations of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) were not affected. . ATP (100 μm) increased cyclic GMP concentration of endothelium‐intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100 μm) and adenosine (100 μm) in endothelium‐intact and ‐denuded vascular preparations. . These results provide evidence that exogenous GTP and guanosine relax precontracted endothelium‐intact and ‐denuded rat mesenteric artery rings by increasing cyclic GMP accumulation. The response to GTP of endothelium‐intact rings can mainly be explained by the release of endothelium‐derived relaxing factor (EDRF), but that of guanosine is only partly due to EDRF, and is a combination of endothelium‐dependent and ‐independent effects. The endothelium‐independent response of GTP and guanosine is a direct, unknown effect on smooth muscle and guanylate cyclase.