Successful curative treatment of severe pulmonary arterial hypertension with luminal obliteration will require a thorough understanding of the mechanism underlying the development and progression of pulmonary vascular lesions. But the cells that obliterate the pulmonary arterial lumen in severe pulmonary arterial hypertension are incompletely characterized. The goal of our study was to evaluate...

Introduction: Chronic mountain sickness (CMS) represents a syndrome of secondary polycythemia along with thrombocytopenia, altered hemorheology, pulmonary and systemic hypertension, and congestive heart failure, occurring due to hypobaric hypoxia-anoxia-induced erythropoiesis reported in both native mountain residents and new climbers after prolonged stays at high and extreme a...

Mutations in genes encoding members of the transforming growth factor (TGF)-beta superfamily have been identified in idiopathic forms of pulmonary arterial hypertension (PAH). The current study examined whether perturbations to the TGF-beta/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH. Expression of the TGF-beta signalling machinery was assessed in ...

Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammato...

BACKGROUND Pulmonary vascular injury by toxins can induce neointimal formation, pulmonary arterial hypertension (PAH), right ventricular failure, and death. We showed previously that simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in pneumonectomized rats injected with the alkaloid toxin monocrotaline. The present study was undertaken to investigate the ...

The mechanisms underlying the pulmonary arterial pressor response to hypoxia have been investigated by studying specimens of pulmonary and systemic vascular smooth muscle and the isolated pulmonary and systemic circulations. Hypoxia caused a unique and reversible loss of potassium and gain in sodium by pulmonary arterial smooth muscle that did not occur in pulmonary veins or systemic arteries. ...

BACKGROUND AND PURPOSE Acute hypoxia is associated with impairment of cerebral autoregulation (CA), but it is unclear if altered CA during prolonged hypoxia is pivotal to the development of cerebral pathology, such as that seen in acute mountain sickness (AMS). This investigation evaluated relationship between CA and AMS over 9 hours of hypobaric hypoxia. METHODS Fifty-five subjects (41 males...

RATIONALE A rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. Increased resting [Ca(2+)](cyt) and enhanced Ca(2+) influx have been implicated in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH). OBJECTIVE We examined whether the extr...

Alterations in the nitric oxide (NO) pathway play a major role in pulmonary arterial hypertension (PAH). L-arginine (LA) and tetrahydrobiopterin (BH4) are main substrates in the production of NO, which mediates pulmonary vasodilation. Administration of either LA or BH4 decrease pulmonary artery pressure (PAP). A combined administration of both may have synergistic effects in the therapy of PAH....