Ohlmann P, Martínez M C, Bucher B, Andriantsitohaina R, Muller B, Schneider F, Stoclet J C
Pharmacologie et physico-chimie des interactions cellulaires et moléculaires, UMR CNRS 7034, Faculté de pharmacie, Université Louis Pasteur, Illkirch, France.
Fundam Clin Pharmacol. 2000 Nov-Dec;14(6):593-600. doi: 10.1111/j.1472-8206.2000.tb00445.x.
In the present study, contractile responses and [3H]-noradrenaline overflow evoked by electrical field stimulation were assessed, respectively, in the small mesenteric artery and in tail artery removed from rats pre-treated with either saline or lipopolysaccharide (LPS). In small mesenteric arteries, LPS treatment did not significantly modify the contractile responses elicited by electrical stimulation, in the absence or in the presence of L-arginine. However, in arteries removed from rats treated with LPS, L-arginine addition produced relaxation of vessels pre-contracted with noradrenaline. The amplification of neurogenic contraction by the nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) was similar in arteries removed from saline and LPS-infused rats. In mesenteric arteries, LPS treatment suppressed the potentiation of the neurogenic responses by the alpha2-adrenoceptor antagonist, yohimbine and by the inhibitor of neuronal uptake of noradrenaline, cocaine. In rat tail artery exposed to L-arginine, LPS treatment produced an increase in [3H]-noradrenaline overflow evoked by electrical stimulation. Altogether, these data suggest that an enhanced noradrenaline release from sympathetic nerves, probably resulting from inhibition of the modulatory effect of both prejunctional alpha2-adrenoceptors and neuronal uptake mechanism, may play a role in the preservation of neurogenic response after LPS treatment despite evidence of the induction of NO synthase.
在本研究中,分别评估了用生理盐水或脂多糖(LPS)预处理的大鼠的小肠系膜动脉和尾动脉中电场刺激诱发的收缩反应以及[3H] - 去甲肾上腺素溢出。在小肠系膜动脉中,无论有无L - 精氨酸,LPS处理均未显著改变电刺激引起的收缩反应。然而,在LPS处理的大鼠所取的动脉中,添加L - 精氨酸可使预先用去甲肾上腺素预收缩的血管舒张。一氧化氮(NO)合酶抑制剂Nω - 硝基 - L - 精氨酸甲酯(L - NAME)对神经源性收缩的增强作用在生理盐水处理和LPS注入大鼠所取的动脉中相似。在肠系膜动脉中,LPS处理抑制了α2 - 肾上腺素能受体拮抗剂育亨宾和去甲肾上腺素神经元摄取抑制剂可卡因对神经源性反应的增强作用。在暴露于L - 精氨酸的大鼠尾动脉中,LPS处理使电刺激诱发的[3H] - 去甲肾上腺素溢出增加。总之,这些数据表明,尽管有证据表明诱导了NO合酶,但交感神经去甲肾上腺素释放增强,可能是由于节前α2 - 肾上腺素能受体和神经元摄取机制的调节作用受到抑制,这可能在LPS处理后神经源性反应的维持中起作用。