Endothelium-dependent sensory non-adrenergic non-cholinergic vasodilatation in rat thoracic aorta: Involvement of ATP and a role for NO

The involvement of non-adrenergic non-cholinergic (NANC) transmitters, such as adenosine 5'-triphosphate (ATP) and nitric oxide (NO), in the neurogeni c relaxation of rat thoracic aorta was investigated in vessel segments susp ended for isometric tension recording by polygraph. Responses to electrical field stimulation (EFS) and exogenous vasodilator w ere investigated in vessels precontracted with 5-hydroxytryptamine. EFS (10 0 V, 2-16 Hz, for 10 s at 3-min intervals), in the presence of guanethidine (10 mu M) and atropine (10 mu M) produced frequency-dependent relaxations. Pretreatment with tetrodotoxin (1 mu M) markedly reduced the relaxation an d desensitization with capsaicin (10 mu M) significantly inhibited the rela xation. Exogenously added ATP caused concentration-dependent relaxations. M echanical removal of the endothelium significantly inhibited EFS- and ATP-i nduced relaxation by 30+/-3% and 37+/-2%, respectively. Pretreatment with a P-1-purinoceptor antagonist, 8-phenyltheophylline (10 mu M) or P-2X-purino ceptor antagonist, Evans blue (10 mu M) did not influence the relaxations t o EFS and exogenously added ATP. In contrast, the P-2Y-purinoceptor antagon ist, basilen blue (100 mu M) markedly reduced the relaxations to EFS by 52/-4% in the endothelium-intact preparations. However, in the endothelium-de nuded preparations and capsaicin-pretreated preparations, basilen blue did not change relaxations elicited by EFS. The NO synthase inhibitor, N-G-nitr o-L-arginine methyl ester (L-NAME, 100 mu M) also significantly inhibited t he relaxations to EFS and ATP by 40+/-6% and 30+/-2%, respectively, in the endothelium-intact preparations but had no effect on the relaxations in the endothelium-denuded preparations or capsaicin-pretreated preparations. In addition, the EFS-induced relaxations were also inhibited 43+/-7% by pretre atment with 1 H-[1,2,4] -oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ; 1 mu M ), soluble guanylate cyclase inhibitor. This study suggests that the NANC nerve system is present in the thoracic a orta of rat, mediating vasodilatation by sensory nerves. ATP, as a neurotra nsmitter released from sensory nerves, activates P-2Y-purinoceptors located on the endothelium and stimulates the NO/cyclic GMP pathway, resulting in vasodilatation.