ABSTRACT
Unlike systemic vascular beds, the pulmonary circulation must accommodate the entire cardiac output, and yet maintain a much lower arterial pressure. This is accomplished by virtue of a very low normal pulmonary vascular resistance (PVR) in physiological conditions. However, elevation of PVR occurs as a consequence of a wide variety of pulmonary, cardiac and systemic disorders (secondary pulmonary hypertension (SPH)) or as a primary disease (primary pulmonary hypertension (PPH)). The role of abnormalities of the L-arginine/NO pathway in the pathogenesis of PH is uncertain. The evidence both supporting and refuting an important contribution is reviewed. In animal models of PH, the evidence suggests a significant impairment of endothelium-dependent dilation, particularly in the larger conduit pulmonary arteries. The evidence is less compelling that reduced NO synthesis or activity is responsible for vasoconstriction and remodeling of smaller resistance vessels. Similarly, the human data is controversial. Although clearly more studies are needed, it might be reasonable to conclude that the clinical experience to date is generally compatible with the more extensive literature from animal studies. Regardless of whether decreased NO activity plays a pathogenic role in PH, there is a good rationale supporting therapeutic strategies to increase pulmonary vascular NO in the treatment of this disorder, and various therapeutic approaches are reviewed.
