Martin P Y, Xu D L, Niederberger M, Weigert A, Tsai P, St John J, Gines P, Schrier R W
Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA.
Am J Physiol. 1996 Mar;270(3 Pt 2):F494-9. doi: 10.1152/ajprenal.1996.270.3.F494.
Nitric oxide (NO) is postulated to mediate the peripheral arterial vasodilation in cirrhosis. However, it is not known which isoform of the nitric oxide synthase (NOS) is involved in the increased production of NO. This study was therefore undertaken to examine the expression of the NOS isoforms in arteries of cirrhotic rats compared with controls. Cirrhosis was induced by CCl4, and vessels were harvested for immunoblots using antibodies against inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS). Endothelial cells were used as controls for ecNOS, and vascular smooth muscle cells treated with lipopolysaccharide or septic rats were used for iNOS controls. The results demonstrated an upregulation of ecNOS in both the aortas and mesenteric arteries of cirrhotic compared with control rats. Chronic inhibition of NOS decreased ecNOS in cirrhotic vessels. Although iNOS mRNA was found by reverse transcription-polymerase chain reaction in arteries of cirrhotic rats, iNOS protein was not detectable by immunoblotting compared with septic rats, suggesting a low vascular level of this isoform. In conclusion, the ecNOS seems to play a major role in the increased NO production in cirrhotic rats, whereas the role of iNOS remains elusive.
一氧化氮（NO）被认为在肝硬化中介导外周动脉血管舒张。然而，尚不清楚哪种一氧化氮合酶（NOS）同工型参与了NO生成的增加。因此，本研究旨在检测与对照组相比，肝硬化大鼠动脉中NOS同工型的表达。用四氯化碳诱导肝硬化，采集血管用于免疫印迹，使用抗诱导型NOS（iNOS）和内皮型组成型NOS（ecNOS）的抗体。内皮细胞用作ecNOS的对照，用脂多糖处理的血管平滑肌细胞或脓毒症大鼠用作iNOS的对照。结果表明，与对照大鼠相比，肝硬化大鼠的主动脉和肠系膜动脉中ecNOS均上调。长期抑制NOS可降低肝硬化血管中的ecNOS。尽管通过逆转录聚合酶链反应在肝硬化大鼠的动脉中发现了iNOS mRNA，但与脓毒症大鼠相比，免疫印迹未检测到iNOS蛋白，表明该同工型的血管水平较低。总之，ecNOS似乎在肝硬化大鼠NO生成增加中起主要作用，而iNOS的作用仍不明确。
