Kelly R A, Smith T W
Cardiovasuclar Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Am J Cardiol. 1996 May 30;77(13):2C-7C. doi: 10.1016/s0002-9149(96)00182-8.
The endothelium functions as a semipermeable membrane separating the blood from the body and allowing the transport of macromolecules from the blood to the interstitial space. The endothelium secretes a number of diffusible substances. These include endothelium-derived relaxing factor (EDRF), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin, in addition to vasoconstrictors including endothelin, angiotensin, and endothelium-derived contracting factor. EDRF is now known to be nitric oxide, or a closely related molecule, which affects signaling by stimulation of soluble guanylate cyclase, causing increased intracellular levels of cyclic guanosine monophosphate (cGMP), in turn leading to relaxation of vascular smooth muscle as well as a variety of additional effects that include altered function of platelets and cardiac myocytes. Nitric oxide can be made available to cellular elements in two ways: by endogenous synthesis via one or more of the three nitric oxide synthases now known to exist in mammalian species; or by exogenous administration of pharmacologic sources of nitric oxide, usually as organic nitrate vasodilators that can be metabolically converted to biologically activated nitric oxide. This process appears to require free sulfydryl groups. The metabolic machinery necessary to convert organic nitrates to a biologically active form exists mainly in the vasculature and not in the myocardium. Numerous studies have demonstrated that the presence of coronary artery disease is associated with interruption of the endogenous production of nitric oxide. Under these circumstances, exogenous nitrates still produce coronary vasodilation as well as relaxation of vascular smooth muscle in the periphery. Other articles in this supplement will focus on the vascular effects of nitric oxide and nitrovasodilators; this article will conclude with a brief discussion of the role of the nitric oxide pathway in the control of cardiac autonomic responsiveness and the potential role of cytokines and the nitric oxide pathway to impair the ability of the myocardium to respond to catecholamines or other stimuli with a normal increase in contractile function.
内皮作为一种半透膜，将血液与身体分隔开，并允许大分子从血液转运至组织间隙。内皮会分泌多种可扩散物质。其中包括内皮源性舒张因子（EDRF）、内皮源性超极化因子（EDHF）和前列环素，此外还有血管收缩剂，如内皮素、血管紧张素和内皮源性收缩因子。现在已知EDRF就是一氧化氮，或一种与之密切相关的分子，它通过刺激可溶性鸟苷酸环化酶来影响信号传导，导致细胞内环磷酸鸟苷（cGMP）水平升高，进而引起血管平滑肌舒张以及包括血小板和心肌细胞功能改变在内的多种其他效应。一氧化氮可通过两种方式供细胞成分利用：通过内源性合成，即经由目前已知存在于哺乳动物体内的三种一氧化氮合酶中的一种或多种；或通过外源性给予一氧化氮的药理学来源，通常是有机硝酸酯类血管扩张剂，它们可经代谢转化为具有生物活性的一氧化氮。这一过程似乎需要游离巯基。将有机硝酸盐转化为生物活性形式所需的代谢机制主要存在于血管系统而非心肌中。大量研究表明，冠状动脉疾病的存在与内源性一氧化氮生成的中断有关。在这种情况下，外源性硝酸盐仍可使冠状动脉舒张以及外周血管平滑肌松弛。本增刊中的其他文章将聚焦于一氧化氮和硝基血管扩张剂的血管效应；本文将以简要讨论一氧化氮途径在控制心脏自主反应性中的作用以及细胞因子和一氧化氮途径在损害心肌对儿茶酚胺或其他刺激产生正常收缩功能增加反应能力方面的潜在作用作为结尾。
