OBJECTIVE Pulmonary arterial hypertension is a progressive pulmonary vascular disorder with high morbidity and mortality. Compelling evidence suggests that receptor tyrosine kinases, such as platelet-derived growth factor (PDGF) are closely involved in the pathogenesis of pulmonary arterial hypertension. We investigated the effects of 2 novel PDGF inhibitors, nilotinib/AMN107 (Abl kinases/PDGF ...

We have investigated the role of angiotensin converting enzyme (ACE) in the development of pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular disease in rats given a single subcutaneous injection of the pyrrolizidine alkaloid monocrotaline. Thirty-six young female Wistar rats were divided into a test group of 27 animals and a control group of nine animals. Each test r...

Adaptation to hypobaric hypoxia is required by animals and human in several physiological and pathological situations. Hypobaric hypoxia is a pathophysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. Identifying the molecular variables playing key roles in this process would be of paramount importan...

BACKGROUND The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed direct field measurements of arterial blood gases in climbers breathing ambient air on Mount Everest. METHODS We obtained samples of arterial blood from 10 climbers during their ascent to and descent from t...

With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review sum...

We banded the left pulmonary artery in rats to investigate, in the same animal, the effect of both increased and decreased flow on the lung vasculature and to determine how these hemodynamic states modify the structural changes produced by a 2-week exposure to hypobaric hypoxia. In unanesthetized rats, pressures were recorded from the main pulmonary artery and aorta via indwelling catheters, ca...

Transforming growth factor-β (TGF-β) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertension was induced by single monocrotaline injection (60 mg/kg) in 75 Wistar rats ...

Hypertensive pulmonary vascular disease is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells, leading to occlusion of pulmonary arterioles, pulmonary hypertension, right ventricular failure, and death. Compounds with antiproliferative effects on vascular endothelial and smooth muscle cells, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase i...

The pulmonary hypertensive response to chronic hypoxia varies markedly among mammalian species. An explanation for this variability was sought by exposing seven species to hypobaric hypoxia (PB equal to 435 mmHg) for 19-48 days. Control animals were studied at 1,600 m (PB equal to 630 mmHg). The pulmonary hypertension that developed varied in the following order of decreasing severity: calf and...

Many pathological conditions, like sleep apnea (SA), preeclampsia, high altitude sickness, and chronic obstructive pulmonary disease, that cause intermittent or chronic hypoxia, are often associated with the development of either systemic or pulmonary hypertension. Mechanisms sensing hypoxia may be important contributors to the development of pulmonary hypertension and to tissue injury and repa...