Corresponding author's email: r.s.baliga@qmul.ac.ukPulmonary hypertension (PH) is a progressive, debilitating disease characterized by increased pulmonary vascular resistance, Rationale: vascular proliferation and remodeling leading to right ventricular failure and death; mortality remains unacceptably high (median survival <3 years). PH is associated with decreased NO bioactivity, and strategies that enhance NO bioavailability/activity are clinically effective (e.g. inhaled NO, phosphodiesterase 5 inhibitors, soluble guanylate cyclase stimulators). Recent evidence demonstrates that provision of inorganic nitrite (NO2-) or nitrate (NO3-) in vivo provides an alternative pathway for endogenous NO generation through sequential reduction to NO, a reaction facilitated under conditions of hypoxia and low pH. Therefore, we investigated whether dietary NO2-and/or NO3-might offer a convenient, inexpensive method of supplementing NO bioactivity and thereby treating PH.Littermate wild-type (WT) and endothelial nitric oxide synthase (eNOS) knockout (KO) mice (male; 20-25g) were exposed to Methods: normobaric hypoxia (10% O2; 21 days) in the absence or presence of dietary KNO (0.6mM) or KNO (15mM & 45mM) supplementation (in
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