Ahlborg G, Lundberg J M
Department of Clinical Physiology, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
J Appl Physiol (1985). 1998 Nov;85(5):1661-6. doi: 10.1152/jappl.1998.85.5.1661.
Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2 and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res. Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin. Physiol. (Colch.) 13: 653-662, 1993), the same increase in mean arterial blood pressure (4%), decreases in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 +/- 3 vs. 23 +/- 2%, P < 0.02), with a total reduction corresponding to 43 +/- 3% (P < 0.01 vs. 23 +/- 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.
血管内皮素受体受到刺激会导致血管收缩，并伴随血管舒张剂前列腺素I2和一氧化氮的产生。在健康男性中，研究了环氧化酶（COX）阻断（静脉注射双氯芬酸）的血管效应以及双氯芬酸给药30分钟后对内皮素-1（ET-1）输注的后续血管收缩反应。COX阻断后，心输出量（7%）、内脏血流量（14%）和肾血流量（12%）下降（均P<0.001）。内脏血流量在30分钟内恢复到基础值。平均动脉血压升高（4%，P<0.001）。内脏葡萄糖输出量下降（22%，P<0.01）。与之前未进行COX阻断时的ET-1输注相比（G.阿尔伯格、E.韦茨伯格和J.M.伦德伯格。《应用生理学杂志》77:121-126，1994年；E.韦茨伯格、G.阿尔伯格和J.M.伦德伯格。《生物化学与生物物理学研究通讯》180:1298-1303，1991年；E.韦茨伯格、G.阿尔伯格和J.M.伦德伯格。《临床生理学》（科尔奇）13:653-662，1993年），后续ET-1输注导致平均动脉血压出现相同幅度的升高（4%），心输出量下降（13%），内脏血流量下降（38%），但内脏葡萄糖输出量无显著变化。肾血流量减少加剧（33±3%对23±2%，P<0.02），总减少量相当于43±3%（与23±3%相比，P<0.01）。我们得出结论，COX抑制会诱导肾和内脏血管收缩。肾血管对ET-1的反应性选择性增加，强调了内源性花生四烯酸代谢产物（即前列腺素I2）对抗ET-1介导的肾血管收缩的重要性。
