Higuchi H, Satoh T
Department of Anaesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Eur J Pharmacol. 1997 Jun 11;328(2-3):175-82. doi: 10.1016/s0014-2999(97)83043-9.
Endothelin-1 (0.1, 1 and 10 nM) induced a significant increase in portal pressure and nitric oxide (NO) release in the isolated rat liver. The endothelin ET(B) receptor agonist, IRL 1620 (Suc-[Glu9,Ala(11,15)]endothelin-1-(8-21)) (0.1, 1 and 10 nM) also elicited a marked increase in portal pressure and NO release. The potency of endothelin-1 was higher than that of IRL 1620. The endothelin ET(A) receptor antagonist, BQ-123 (cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu)) (1 and 10 microM), had no effect on the endothelin-1-induced change in portal pressure and NO current. In contrast, the endothelin ET(B) receptor antagonist, BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-1-++ +methoxycarbonyltryptophanyl-D-norleucine) (1 and 10 nM), attenuated the endothelin-1-induced change in portal pressure and NO current. Administration of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, completely abolished the endothelin-1- or IRL 1620-induced NO release. L-NMMA enhanced the increase in portal pressure and decrease in O2 consumption caused by endothelin-1. These results indicated that endothelin ET(B) receptors mediate both vasoconstriction and NO release and that NO plays a significant role in stabilizing microcirculation in isolated perfused rat liver.
内皮素 -1（0.1、1和10纳摩尔）可使离体大鼠肝脏的门静脉压力和一氧化氮（NO）释放显著增加。内皮素ET(B)受体激动剂IRL 1620（Suc-[Glu9,Ala(11,15)]内皮素-1-(8 - 21)）（0.1、1和10纳摩尔）也可引起门静脉压力和NO释放显著增加。内皮素-1的效力高于IRL 1620。内皮素ET(A)受体拮抗剂BQ - 123（环（-D-色氨酸-D-天冬氨酸-脯氨酸-D-缬氨酸-亮氨酸））（1和10微摩尔）对内皮素-1引起的门静脉压力变化和NO电流无影响。相反，内皮素ET(B)受体拮抗剂BQ - 788（N-顺式-2,6-二甲基哌啶羰基-L-γ-甲基-亮氨酰-D-1-甲氧基羰基色氨酰-D-正亮氨酸）（1和10纳摩尔）可减弱内皮素-1引起的门静脉压力变化和NO电流。给予NO合酶抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）可完全消除内皮素-1或IRL 1620诱导的NO释放。L-NMMA增强了内皮素-1引起的门静脉压力升高和氧消耗降低。这些结果表明，内皮素ET(B)受体介导血管收缩和NO释放，且NO在稳定离体灌注大鼠肝脏的微循环中起重要作用。
