Premium
Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery
Author(s) -
Vuorinen Pauli,
Pörsti Ilkka,
MetsäKetelä Timo,
Manninen Vesa,
Vapaatalo Heikki,
Laustiola Kai E.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14246.x
Subject(s) - adenosine , guanosine , gtp' , nucleotide , mesenteric arteries , endothelium , vascular tone , medicine , endocrinology , chemistry , artery , biology , vasodilation , anatomy , biochemistry , enzyme , gene
Summary1 . 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. 2 . GTP (10 μ m −1 m m ) 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 N G ‐nitro l ‐arginine methyl ester ( l ‐NAME, 330 μ m ) which attenuation was reversed with l ‐arginine (1 m m ). 3 . Guanosine (10 μ m −1 m m ) 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 μ m ). 4 . ATP (1 μ m −1 m m ) and adenosine (10 μ m −1 m m ) dose‐dependently relaxed endothelium‐intact and ‐denuded artery rings. The responses were more pronounced in endothelium‐intact vascular preparations. 5 . GTP (100 μ m ) and guanosine (100 μ m ) 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. 6 . ATP (100 μ m ) increased cyclic GMP concentration of endothelium‐intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100 μ m ) and adenosine (100 μ m ) in endothelium‐intact and ‐denuded vascular preparations. 7 . 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.