Blanco-Rivero Javier, Aller Ma Angeles, Arias Jaime, Ferrer Mercedes, Balfagón Gloria
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Clin Sci (Lond). 2009 Sep 7;117(10):365-74. doi: 10.1042/CS20080499.
In the present study, we have analysed both the effect of long-term portal hypertension on the vasomotor response to acetylcholine in rat aorta and the mechanism involved in this response. For this purpose, sham-operated rats and rats with pre-hepatic PH (portal hypertension; triple partial portal vein ligation) were used at 21 months after surgery. The participation of NO and COX (cyclo-oxygenase) derivatives in the vasodilator response elicited by acetylcholine after incubation with L-NAME (NG-nitro-L-arginine methyl ester), indomethacin, SC-560, NS-398, tranylcypromine and furegrelate, was analysed. NO, TXB2 (thromboxane B2) and 6-keto PGF1alpha (prostaglandin F1alpha) release were measured. In addition, SNP (sodium nitroprusside), U-46619, PGI2 and forskolin vasomotor responses were analysed. COX-1 and COX-2 expression was also determined. The acetylcholine-induced vasodilating response was higher in rats with PH. TXA2 and NO release, and SNP and U-46619 sensitivity were similar in both groups. PGI2 release was not modified by portal hypertension, but vasodilator responses to this prostanoid and to forskolin were higher in rats with PH. COX-1 and COX-2 expression remained unmodified by surgery. In conclusion, increased vasodilation to acetylcholine is maintained in long-term PH. Although the participation of endothelial NO remained unmodified, the COX-2 derivative PGI2 does participate through an increased vasodilator response.
在本研究中，我们分析了长期门静脉高压对大鼠主动脉血管运动反应的影响以及该反应所涉及的机制。为此，在手术后21个月使用假手术大鼠和肝前性门静脉高压（门静脉高压；三重部分门静脉结扎）大鼠。分析了在与L-精氨酸甲酯（L-NAME）、吲哚美辛、SC-560、NS-398、反苯环丙胺和呋格雷酯孵育后，一氧化氮（NO）和环氧化酶（COX）衍生物在乙酰胆碱引发的血管舒张反应中的参与情况。测量了NO、血栓素B2（TXB2）和6-酮前列腺素F1α（PGF1α）的释放。此外，分析了硝普钠（SNP）、U-46619、前列环素（PGI2）和福斯高林的血管运动反应。还测定了COX-1和COX-2的表达。门静脉高压大鼠中乙酰胆碱诱导的血管舒张反应更高。两组中TXA2和NO的释放以及对SNP和U-46619的敏感性相似。门静脉高压未改变PGI2的释放，但门静脉高压大鼠对该前列腺素和福斯高林的血管舒张反应更高。手术未改变COX-1和COX-2的表达。总之，长期门静脉高压时对乙酰胆碱的血管舒张增加得以维持。尽管内皮型NO的参与未改变，但COX-2衍生物PGI2确实通过增加血管舒张反应而参与其中。
