Nitric Oxide in Pulmonary Hypertension

  • J. O. C. AulerJr.


Nitric oxide (NO) has mainly been seen as a toxic agent associated with air pollution. Recently it has been recognized as a primary endogenous mediator of important physiologic processes. Both artery and vein are able to release endothelium-derived relaxing factor (EDRF) in response to different vasodilators (1, 2). Among several functions, the vascular endothelium, which encircles the blood, contributes to the control of vascular tone by releasing compounds that mediate contraction or relaxation of the underlying vascular smooth muscle (3, 4). The endothelium synthesizes vasodilator substances such as prostacyclin, endothelium-derived relaxing factor or nitric oxide (NO) (5, 6) as well as endothelin(s) and endothelium-derived contracting factor which promotes vasoconstriction (3). In response to several stimuh or mediators, the endothehal L-arginine NO pathway is activated by contact with the blood, in addition to receptor utilized mechanisms activated by shear stress, acetylcholine, ADP, bradykinin, substance P, histamine, and platelet-derived products (7). NO diffuses into the smooth muscle cells where it activates the soluble guanylate cyclase to generate cychc GMP, the second messenger mediating relaxation (6, 8, 9). Endogenous NO seems to be continuously released for accurate regulation of vascular tone. Substances such as acetylcholine or bradykinin are considered as endothelium-dependent dilators and therapeutic nitrates which directly activate soluble guanylate cyclase by releasing NO from their molecules are considered as endothelium-independent dilators. NO is also considered an inhibitor of platelet aggregation, contributing to the vasodilator properties of prostacyclin (7, 10). Vascular smooth muscle relaxation and cyclic GMP accumulation due to the action of several chemical substances on the endothelium are attributed to the release of NO (11, 12). The central role of the endothelium in mediating vessel tone has become of paramount importance since knowing of acetylcholine dependence on EDRF release. Endothehal dysfunction in a number of vascular diseases may be related to an attenuated acethylcholine response and decreased NO release, which may contribute to pulmonary hypertension (13, 14).


Nitric Oxide Nitric Oxide Pulmonary Hypertension Pulmonary Vascular Resistance Hypoxic Pulmonary Vasoconstriction 
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© Springer-Verlag Italia, Milano 1996

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  • J. O. C. AulerJr.

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