Endothelium-dependent and -independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery.
1. 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 microM-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 microM) which attenuation was reversed with L-arginine (1 mM). 3. Guanosine (10 microM-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 microM). 4. ATP (1 microM-1 mM) and adenosine (10 microM-1 mM) dose-dependently relaxed endothelium-intact and -denuded artery rings. The responses were more pronounced in endothelium-intact vascular preparations. 5. GTP (100 microM) and guanosine (100 microM) 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 microM) increased cyclic GMP concentration of endothelium-intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100 microM) and adenosine (100 microM) 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.
Vuorinen
P
P
Department of Biomedical Sciences, University of Tampere, Finland.
Pörsti
I
I
Metsä-Ketelä
T
T
Manninen
V
V
Vapaatalo
H
H
Laustiola
K E
KE
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006151:Guanosine / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019335:Nitroarginine; D009711:Nucleotides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009711:Nucleotides; D006151:Guanosine; D019335:Nitroarginine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D001120:Arginine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000241:Adenosine; D000109:Acetylcholine