Chronic hypoxia (CH) increases pulmonary endothelial nitric oxide synthase (eNOS) protein levels in adult rats but decreases eNOS protein levels in neonatal pigs. We hypothesized that this differing response to CH is due to developmental rather than species differences. Adult and neonatal rats were placed in either hypobaric hypoxia or normoxia for 2 wk. At that time, body weight, hematocrit, p...

Background—Hypoxia induces an inflammatory response in the lung manifested by alternative activation of macrophages with elevation of proinflammatory mediators that are critical for the later development of hypoxic pulmonary hypertension. Mesenchymal stromal cell transplantation inhibits lung inflammation, vascular remodeling, and right heart failure and reverses hypoxic pulmonary hypertension ...

BACKGROUND Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined. METHODOLOGY/PRINCIPAL...

Previous studies have suggested an association between uric acid (UA) and the severity of pulmonary arterial hypertension (PAH), but it is unknown whether UA contributes to disease pathogenesis. The aim this study was determine prognostic value circulating in era current management PAH investigate role vascular remodelling. Serum levels were determined idiopathic, heritable or anorexigen at bas...

BACKGROUND Recent evidence suggests that bone marrow (BM)-derived cells may differentiate into vascular cells that participate in arterial repair and/or lesion formation. However, it remains uncertain whether BM-derived cells also can participate in vascular remodeling associated with pulmonary arterial hypertension. METHODS AND RESULTS The BM of Sprague-Dawley rats was reconstituted with tha...

INTRODUCTION Skepticism exists about whether normobaric and hypobaric hypoxic exposures are equivalent. We have evaluated if physiological differences between the two environments would translate into actual differences in hypoxia symptoms. METHODS We exposed 20 subjects to 5-min 25,000-ft (7620-m) equivalent environments in an altitude chami ber and then in a ground-level portable reduced-ox...

The pyrrolizidine alkaloid monocrotaline produces pulmonary inflammation, hemorrhage, fibrosis, and hypertension. In rats, monocrotaline pneumotoxicity can be ameliorated by cotreatment with inhibitors of angiotensin converting enzyme (ACE), such as CL242817. In the present study, serum and urine copper (Cu) concentrations were evaluated as indices of cardiopulmonary injury in rats sacrificed a...

Cell-free hemoglobin (Hb) exposure may be a pathogenic mediator in the development of pulmonary arterial hypertension (PAH), and when combined with chronic hypoxia the potential for exacerbation of PAH and vascular remodeling is likely more pronounced. We hypothesized that Hb may contribute to hypoxia-driven PAH collectively as a prooxidant, inflammatory, and nitric oxide (NO) scavenger. Using ...

Body surface potential mapping (BSPM) was performed in female rats with pulmonary arterial hypertension (PAH) induced by a single subcutaneous injection monocrotaline (60 mg/kg body wt). Analysis of data was produced by equipotential momentous maps during ventricle depolarization. In rats with monocrotaline-induced PAH was confirmed hypertrophy of the right ventricle. It is reflected on equipot...

UNLABELLED The ATP-binding cassette transporter MRP4 (encoded by ABCC4) regulates membrane cyclic nucleotides concentrations in arterial cells including smooth muscle cells. MRP4/ABCC4 deficient mice display a reduction in smooth muscle cells proliferation and a prevention of pulmonary hypertension in response to hypoxia. We aimed to study gene transfer of a MRP4/ABCC4 silencing RNA via intratr...