Gustafsson L E, Persson M G, Wei S Z, Wiklund N P, Elias Y
Department of Physiology and Pharmacology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
J Cardiovasc Pharmacol. 1994 Apr;23(4):612-7. doi: 10.1097/00005344-199404000-00013.
We investigated the role of nitric oxide (NO) in the mediation of nerve stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and vascular resistance were measured in pentobarbital-anesthetized, paralyzed, and guanethidine-treated rabbits. Centrifugal electrical stimulation of the sciatic nerve bundle induced reproducible, frequency-, voltage-, and pulse duration-dependent decrements in vascular resistance. The tachykinin antagonist CP-96,345 (1 mg/kg intravenously, i.v.) attenuated the vasodilation induced by intraarterially (i.a.) administered substance P but not by adenosine. Furthermore, CP-96,345 attenuated the decrease in vascular resistance in response to nerve stimulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting resistance (p < 0.005), without affecting basal vascular resistance. An inhibitor of NO formation, N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.v.), increased vascular resistance from 6.1 +/- 0.5 to 9.1 +/- 1.2 resistance units (p < 0.05) and significantly attenuated the vascular response to i.a. administered substance P but not adenosine. Finally, nerve stimulation-induced reduction in vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0% of control (p < 0.001). These findings suggest that tachykinins and NO are involved in mediation of vasodilation in response to the present type of nerve stimulation. The data are consistent with the hypothesis that NO is produced subsequent to neural release of tachykinin-type transmitter(s).
我们研究了一氧化氮（NO）在介导神经刺激引起的骨骼肌血管舒张中的作用。在戊巴比妥麻醉、麻痹并用胍乙啶处理的兔子中测量后肢血流量和血管阻力。对坐骨神经束进行离心电刺激可引起血管阻力出现可重复的、频率、电压和脉冲持续时间依赖性的降低。速激肽拮抗剂CP-96,345（静脉注射1mg/kg）减弱了动脉内（i.a.）给予P物质引起的血管舒张，但对腺苷引起的血管舒张无影响。此外，CP-96,345减弱了对神经刺激的血管阻力降低，从对照静息阻力的22.9±3.2%降至4.5±4.1%（p<0.005），而不影响基础血管阻力。NO生成抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME，静脉注射30mg/kg）使血管阻力从6.1±0.5个阻力单位增加到9.1±1.2个阻力单位（p<0.05），并显著减弱了对动脉内给予P物质的血管反应，但对腺苷无影响。最后，L-NAME减弱了神经刺激引起的血管阻力降低，从对照的22.6±2.7%降至7.0±1.0%（p<0.001）。这些发现表明，速激肽和NO参与了对当前类型神经刺激的血管舒张介导。数据与速激肽型递质神经释放后产生NO的假说一致。
