Lavallée M, Takamura M, Parent R, Thorin E
Department of Physiology, Faculty of Medicine, Université de Montréal, and Institut de Cardiologie de Montréal, Montréal, Québec, Canada.
Heart Fail Rev. 2001 Dec;6(4):265-76. doi: 10.1023/a:1011448007222.
Several lines of evidence indicate that nitric oxide (NO) impairs endothelin (ET) production/action in vitro. Acute pressor responses caused by the blockade of NO formation with arginine analogues in vivo are blunted by selective ET(A) or dual ET(A)/ET(B) receptor blockade whereas blockade of NO formation magnifies ET-induced constriction of various vascular territories. Given that ET receptor blockade has normally limited effects on mean arterial pressure, the reversal of pressor responses caused by the blockade of NO formation with ET receptor blockade most likely reflects a significant crosstalk between NO and ET. Suppression of NO formation also leads to significant increases in ET production caused by agents targeting the endothelium, such as acetylcholine and thrombin. In addition, the inhibitory effect of shear stress on endothelial cells ET production also involves NO as an intermediate.Paradoxically, chronic exposure to organic nitrates which causes nitrate tolerance leads to an augmented vascular ET content. An increased angiotensin II (AII) production is apparently pivotal in this process. This article reviews observations pointing to the importance of NO/ET interactions as a fundamental and common regulatory mechanism shared across species. As a consequence of this crosstalk between NO and ET, experimental strategies designed to assess endothelial NO-dependent activity by the blockade of NO formation may be mitigated by magnified ET-dependent influences.
多条证据表明，一氧化氮（NO）在体外会损害内皮素（ET）的生成/作用。体内用精氨酸类似物阻断NO生成所引起的急性升压反应，会因选择性ET(A)受体阻断或ET(A)/ET(B)双受体阻断而减弱，而阻断NO生成会放大ET诱导的各种血管区域的收缩。鉴于ET受体阻断对平均动脉压的影响通常有限，用ET受体阻断来逆转因阻断NO生成所引起的升压反应，很可能反映了NO与ET之间存在显著的相互作用。抑制NO生成还会导致由靶向内皮的药物（如乙酰胆碱和凝血酶）引起的ET生成显著增加。此外，剪切应力对内皮细胞ET生成的抑制作用也涉及NO作为中间介质。矛盾的是，长期接触导致硝酸盐耐受的有机硝酸盐会使血管ET含量增加。血管紧张素II（AII）生成增加显然在这一过程中起关键作用。本文综述了一些观察结果，这些结果表明NO/ET相互作用作为一种跨物种共享的基本且常见的调节机制具有重要意义。由于NO与ET之间的这种相互作用，旨在通过阻断NO生成来评估内皮NO依赖性活性的实验策略，可能会因放大的ET依赖性影响而受到影响。
