Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension

Abstract

SPECIFIC AIMSBased on its critical role in mediating vasodilation, a decrease of nitric oxide (NO) has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), a rare disease characterized by impaired regulation of pulmonary hemodynamics and vascular growth. Although NO levels are lower in PAH lungs than healthy controls, whether a decrease of NO is due to decreased expression of NO synthase (NOS) proteins has been controversial. Our aim was to determine the mechanisms for the low NO in pulmonary hypertension. We evaluated expression of NOS and factors regulating NOS activity (i.e., substrate arginine, arginase expression and activity, and endogenous inhibitors of NOS in patients with PAH and healthy controls).PRINCIPAL FINDINGS1. Clinical characteristicsNineteen healthy controls and 18 PAH World Health Organization class 1 individuals, 16 of whom were diagnosed with primary pulmonary hypertension (PPH; PAH subclass 1.1), participated in the study. Clinical characteristics of PAH pati...