Büyükafşar Kansu, Arikan Onur, Ark Mustafa, Kubat Havva, Ozveren Elif
Department of Pharmacology Medical Faculty Mersin University Campus Yenişehir 33169 Mersin, Turkey.
Eur J Pharmacol. 2004 Sep 13;498(1-3):211-7. doi: 10.1016/j.ejphar.2004.07.092.
Effects of bacterial lipopolysaccharide (Escherichia coli serotype, 055:B5, 20 mg kg(-1), i.p., for 6 h) and a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate, Y-27632 (10(-9)-10(-5) M) were investigated on the contractile responses of the rat mesenteric artery to phenylephrine (10(-9)-3 x 10(-5) M), angiotensin-2 (10(-10)-10(-6) M) and endothelin-1 (10(-10)-10(-7) M). Moreover, alteration in the level of Rho-kinase (ROCK-2) expression was examined in the superior mesenteric artery obtained from saline- and lipopolysaccharide-treated rats by Western blotting. Endotoxemic rat mesenteric rings exhibited no different contractions to phenylephrine and angiotensin-2 but augmented contractile activity to endothelin-1. In the mesenteric artery obtained from the endotoxemic rats, acetylcholine-induced vasorelaxation did not differ; pD2 value for acetylcholine was 7.85+/-0.12 in the endotoxemic rings; however, it was 7.81+/-0.15 in the control rings (P>0.05). Y-27632 induced relaxation, which was the same in the control arteries as in endotoxemic ones when contracting agent was phenylephrine. However, when endothelin-1 was used to precontract the rings, Y-27632 produced enhanced relaxation in endotoxemic vessels. pD2 values for Y-27632 were, respectively, 7.69+/-0.12 and 8.20+/-0.10 in control and endotoxemic rings precontracted by endothelin-1 (10(-8) M) (P<0.01). Moreover, Y-27632 (10(-5) M) suppressed the contraction induced by angiotensin-2 (10(-10)-10(-6) M). Western blot analysis revealed that Rho-kinase was upregulated significantly in the mesenteric artery obtained from the rats treated with LPS for 6 h. In addition, serum NO2-/NO3- level, which was detected by Griess method, was 10.0+/-1.4 microM in endotoxemic rats; however, it was 6.6+/-0.5 microM in control (P<0.05). Taken together, these results show that the expression of the contractile protein Rho-kinase could be upregulated in endotoxemic mesenteric artery and this upregulation may be coincided with an enhanced contraction to endothelin-1 but not phenylephrine and angiotensin-2.
研究了细菌脂多糖（大肠杆菌血清型，055:B5，20毫克/千克，腹腔注射，持续6小时）和一种Rho激酶抑制剂（(+)-(R)-反式-4-(1-氨基乙基)-N-(4-吡啶基)环己烷甲酰胺二盐酸盐一水合物，Y-27632，10⁻⁹ - 10⁻⁵ 摩尔/升）对大鼠肠系膜动脉对去氧肾上腺素（10⁻⁹ - 3×10⁻⁵ 摩尔/升）、血管紧张素-2（10⁻¹⁰ - 10⁻⁶ 摩尔/升）和内皮素-1（10⁻¹⁰ - 10⁻⁷ 摩尔/升）收缩反应的影响。此外，通过蛋白质免疫印迹法检测了从生理盐水处理和脂多糖处理大鼠获取的肠系膜上动脉中Rho激酶（ROCK-2）表达水平的变化。内毒素血症大鼠的肠系膜环对去氧肾上腺素和血管紧张素-2的收缩反应无差异，但对内皮素-1的收缩活性增强。在内毒素血症大鼠的肠系膜动脉中，乙酰胆碱诱导的血管舒张无差异；内毒素血症环中乙酰胆碱的pD2值为7.85±0.12；然而，对照环中为7.81±0.15（P>0.05）。当收缩剂为去氧肾上腺素时，Y-27632诱导的舒张在对照动脉和内毒素血症动脉中相同。然而，当用内皮素-1预收缩环时，Y-27632在内毒素血症血管中产生增强的舒张。在内皮素-1（10⁻⁸ 摩尔/升）预收缩的对照环和内毒素血症环中，Y-27632的pD2值分别为7.69±0.12和8.20±0.10（P<⁰.⁰¹）。此外，Y-27632（10⁻⁵ 摩尔/升）抑制了血管紧张素-2（10⁻¹⁰ - 10⁻⁶ 摩尔/升）诱导的收缩。蛋白质免疫印迹分析显示，在经脂多糖处理6小时的大鼠获取的肠系膜动脉中，Rho激酶显著上调。此外，通过格里斯法检测的血清NO₂⁻/NO₃⁻ 水平，内毒素血症大鼠为10.0±1.4微摩尔；然而，对照为6.6±0.5微摩尔（P<0.05）。综上所述，这些结果表明，收缩蛋白Rho激酶的表达在内毒素血症肠系膜动脉中可能上调，这种上调可能与对内皮素-1而非去氧肾上腺素和血管紧张素-2的收缩增强有关。
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