May C N, Mathai M L, McDougall J G, Whitworth J A
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
Am J Hypertens. 1993 Oct;6(10):837-43. doi: 10.1093/ajh/6.10.837.
Infusion of endothelin-1 (ET-1) (2000 pmol/h) into conscious sheep for 6 days caused a sustained increase in mean arterial pressure (MAP) of 19 +/- 1 mm Hg. This response was mediated by the vasoconstrictor effect of ET-1 and was accompanied by a fall in cardiac output. Plasma renin concentration fell throughout the infusion and atrial natriuretic peptide was increased on day 1 of ET-1 infusion. Hematocrit dramatically increased, probably mainly due to plasma loss resulting from the ET-1-induced increased capillary hydrostatic pressure. To determine whether increased pressor responsiveness to ET-1 played a role in the rise in MAP caused by corticotropin (ACTH), the responses to bolus doses of ET-1 were evaluated before ACTH and on days 3 and 5 of ACTH infusion (5 micrograms/kg/day). ACTH increased MAP from 71 +/- 2 to 87 +/- 3 mm Hg. On the control day ET-1 (400, 1200, and 2000 pmol) increased MAP by 5 +/- 1, 18 +/- 6 and 35 +/- 11 mm Hg, respectively. No initial vasodilation occurred. The responses to all doses of ET-1 were similar during ACTH infusion. Plasma levels of ET-1 did not increase during ACTH infusion. These results demonstrate that long-term infusion of ET-1 caused a sustained increase in blood pressure. There was no evidence that the sensitivity or responsiveness to ET-1 were altered during infusion of ACTH. In conclusion, ET-1 could play a role in the pathogenesis of hypertension but does not appear to be involved in the increase in blood pressure caused by ACTH.
向清醒的绵羊体内持续6天输注内皮素-1（ET-1）（2000皮摩尔/小时），可使平均动脉压（MAP）持续升高19±1毫米汞柱。这种反应是由ET-1的血管收缩作用介导的，同时伴有心输出量下降。在整个输注过程中，血浆肾素浓度下降，而在ET-1输注第1天时，心房利钠肽增加。血细胞比容显著升高，可能主要是由于ET-1诱导的毛细血管流体静压升高导致血浆丢失。为了确定对ET-1的升压反应性增加是否在促肾上腺皮质激素（ACTH）引起的MAP升高中起作用，在输注ACTH前以及输注ACTH（5微克/千克/天）的第3天和第5天评估对大剂量ET-1的反应。ACTH使MAP从71±2毫米汞柱升高至87±3毫米汞柱。在对照日，ET-1（400、1200和2000皮摩尔）分别使MAP升高5±1、18±6和35±11毫米汞柱。未出现初始血管舒张。在输注ACTH期间，对所有剂量ET-1的反应相似。在输注ACTH期间，ET-1的血浆水平未升高。这些结果表明，长期输注ET-1会导致血压持续升高。没有证据表明在输注ACTH期间对ET-1的敏感性或反应性发生改变。总之，ET-1可能在高血压发病机制中起作用，但似乎不参与ACTH引起的血压升高。
