Russell J A, Roberts J M
Department of Physiology, State University of New York, Buffalo 14214.
Pulm Pharmacol. 1991;4(2):67-72. doi: 10.1016/0952-0600(91)90054-7.
An endothelium-derived 21-residue peptide, endothelin, has been shown to be a constrictor of arteriolar smooth muscle. This study investigated the effect of endothelin on isolated pulmonary veins and arteries using tissue bath techniques. Endothelin elicited concentration-dependent contractions and maximal responses were equal in magnitude to those of phenylephrine (PE) or norepinephrine (NE). Responses to endothelin were long lasting and persisted despite repeated washing. The following agents had no significant effect on endothelin-induced contractions: FPL 55712 (1 microM), indomethacin (10 microM), methysergide (3 microM), phentolamine (3 microM), pyrilamine (3 microM) and the putative thromboxane A2 receptor antagonist SQ 29,548 (3 microM). Moreover, removal of the endothelium did not alter responses to endothelin. Isoproterenol, forskolin, and 8-bromo-cAMP had a differential inhibitory effect on matched contractions induced by endothelin and the putative thromboxane A2 receptor agonist U-46619. Isoproterenol (0.1 microM) relaxed endothelin and U-46619 contractions by 2 +/- 1% and 74 +/- 5%, respectively; forskolin (3 microM) by 12 +/- 3% and 84 +/- 9%, respectively and 8-bromo-cAMP (10 mM) by 23 +/- 8% and 82 +/- 9%, respectively. Likewise, 10 microM sodium nitroprusside relaxed endothelin contractions by 32 +/- 4% and PE contractions by 80 +/- 9%. Endothelin is a very potent pulmonary vasoconstrictor that appears to have a direct effect on vascular smooth muscle. Compared to U-46619 or PE, endothelin-induced contractions are highly resistant to relaxing agents that increase either cAMP or cGMP. Moreover, resistance to cAMP does not appear to involve inhibition of adenylate cyclase.
一种内皮衍生的由21个氨基酸残基组成的肽，即内皮素，已被证明是小动脉平滑肌的收缩剂。本研究使用组织浴技术研究了内皮素对离体肺静脉和动脉的影响。内皮素引起浓度依赖性收缩，最大反应幅度与去氧肾上腺素（PE）或去甲肾上腺素（NE）的最大反应幅度相等。对内皮素的反应持续时间长，尽管反复冲洗仍持续存在。以下药物对内皮素诱导的收缩无显著影响：FPL 55712（1微摩尔）、吲哚美辛（10微摩尔）、甲基麦角新碱（3微摩尔）、酚妥拉明（3微摩尔）、吡拉明（3微摩尔）以及假定的血栓素A2受体拮抗剂SQ 29548（3微摩尔）。此外，去除内皮并不改变对内皮素的反应。异丙肾上腺素、福斯高林和8-溴-cAMP对内皮素和假定的血栓素A2受体激动剂U-46619诱导的匹配收缩有不同的抑制作用。异丙肾上腺素（0.1微摩尔）分别使内皮素和U-46619收缩松弛2±1%和74±5%；福斯高林（3微摩尔）分别使内皮素和U-46619收缩松弛12±3%和84±9%；8-溴-cAMP（10毫摩尔）分别使内皮素和U-46619收缩松弛23±8%和82±9%。同样，10微摩尔硝普钠使内皮素收缩松弛32±4%，使PE收缩松弛80±9%。内皮素是一种非常强效的肺血管收缩剂，似乎对血管平滑肌有直接作用。与U-46619或PE相比，内皮素诱导的收缩对增加cAMP或cGMP的松弛剂具有高度抗性。此外，对cAMP的抗性似乎不涉及腺苷酸环化酶的抑制。
