**Author details**

Rajamma Mathew\*

Address all correspondence to: rajamma\_mathew@NYMC.edu

Departments of Pediatrics and Physiology, New York Medical College, Valhalla, NY, USA

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**Chapter 4**

**Nitric Oxide in Pathophysiology and**

Junko Maruyama, Ayumu Yokochi, Erquan Zhang,

All conditions causing pulmonary hypertension (PH) are characterized by three major changes in the pulmonary vasculature: vasoconstriction, vascular remodeling, and thrombosis [1,2,3]. Vascular remodeling includes muscularization of normally non-muscular peripheral pulmo‐ nary arteries, increase in medial wall thickness of muscular arteries, and increase in vascular connective tissue such as collagen and elastin [1,2,3]. Imbalance of vasoconstrictive and vasodilatory mediators might explain the increased vascular tone [1,2,3]. Endothelial cells synthesize and release prostacylin and nitric oxide for vasodilation as well as endothelin and thromboxane for vasoconstriction. Approved treatments for pulmonary arterial hypertension (PAH) include prostacyclins, endothelin receptor blockers, and phosphodiesterase-5 inhibitors as well as inhaled NO for persistent pulmonary hypertension of the neonate (PPHN) [2].

Studies have demonstrated that short- and long-term NO inhalation improves arterial oxygenation and reduces pulmonary artery (PA) pressure in animal models of PH [4,5,6,7,8,9,10] and clinical disease such as post-operative congenital heart disease [11,12], chronic obstructive pulmonary disease (COPD) [13], pulmonary fibrosis [14], and acute respiratory distress syndrome (ARDS) [15]. In chronic hypoxia-induced PH in rats, we showed that low-dose NO (less than 5ppm) induces a submaximal reduction in pulmonary artery pressure, which does not correlate with the severity of pulmonary vascular changes [4]. Clinically, the effect of inhaled NO is based on pulmonary vasorelaxation. In experimental settings, NO inhibits vascular smooth muscle cell proliferation directly through regulating protein kinases modulating gene expression for cell growth and/or indirectly through reducing pressure on the vascular cells by cyclic guanosine-3',5'-monophosphate (cGMP) dependent

> © 2013 Maruyama et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 Maruyama et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Hirofumi Sawada and Kazuo Maruyama

http://dx.doi.org/10.5772/55680

**1. Introduction**

Additional information is available at the end of the chapter

**Treatment of Pulmonary Hypertension**

**Chapter 4**
