Sastre Esther, Caracuel Laura, Prieto Isabel, Llévenes Pablo, Aller M Ángeles, Arias Jaime, Balfagón Gloria, Blanco-Rivero Javier
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, España.
Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España.
Sci Rep. 2016 Aug 3;6:31076. doi: 10.1038/srep31076.
We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis.
我们评估了肝胆汁淤积(LC),一种失代偿性肝硬化模型,对大鼠肠系膜上动脉(SMA)交感神经、感觉神经和氮能神经功能产生的可能改变。在LC动物中,对电场刺激(EFS)的血管收缩反应更强。α-肾上腺素能受体拮抗剂酚妥拉明和P2嘌呤受体拮抗剂苏拉明在LC动物中比在对照动物中更能降低这种反应。非特异性一氧化氮合酶(NOS)L-NAME和降钙素基因相关肽(CGRP)(8-37)在LC中比在对照节段中更强烈地增强了对EFS的血管收缩反应。在LC节段中,对去甲肾上腺素(NA)或CGRP的血管舒缩反应更大,而NO类似物DEA-NO在两个实验组中诱导了相似的血管舒张。NA的释放没有改变,而ATP、亚硝酸盐和CGRP在LC节段中的释放增加。α1肾上腺素能受体、Rho激酶(ROCK)1和2以及总肌球蛋白磷酸酶(MYPT)的表达没有改变,而α2B肾上腺素能受体、nNOS表达以及nNOS和MYPT的磷酸化在LC中增加。总之,这些改变可能抵消在失代偿性肝硬化晚期观察到的内脏血管舒张增加。