What is the clinical evidence from this study?

Study design: Other. Population: Pulmonary hypertension. Intervention: Chronic hypoxia vs. Normoxia (20% O2). Primary outcome: Time-dependent phenotypic and contractile changes of pulmonary artery.

January 1, 2009Open Access

Time-Dependent Phenotypic and Contractile Changes of Pulmonary Artery in Chronic Hypoxia–Induced Pulmonary Hypertension

Key Result

Chronic hypoxia induced a transient peak in pulmonary arterial smooth muscle cell proliferation at 1 week, followed by a sustained increase in basal active tonus and decreased absolute contractility.

Structured PICO

Population

Male Sprague-Dawley rats at 7 weeks of age exposed to normobaric hypoxia (10% O2) or normoxia for 1-4 weeks to study pulmonary hypertension.

Intervention

Normobaric hypoxia (10% O2) for 1-4 weeks

Comparator

Normoxia (room air, 20% O2) for 1-4 weeks

Outcome

Phenotypic and contractile changes in pulmonary arterial smooth muscle cells (PASMCs), including proliferative activity, actin expression ratio, and contractilitysurrogate

Chronic hypoxia induces a phenotypic switch in pulmonary arterial smooth muscle cells from a contractile to a synthetic state, contributing to vascular remodeling and increased basal tonus in pulmonary hypertension.

Limitations

Pulmonary pressure was not measured directly
Further investigations are necessary to clarify the intrinsic negative regulatory system involved in hypoxia-induced increment of basal active tonus

Abstract

Phenotypic and contractile changes in pulmonary arterial smooth muscle cells (PASMCs) were examined in rats with pulmonary hypertension induced by hypoxia. Exposure to hypoxia induced pulmonary hypertension within 1-4 weeks. Staining with BrdU revealed that proliferative activities of PASMCs peaked at 1 week of hypoxic exposure, and then moderate proliferative activity was maintained for the next 2-4 weeks. The beta-actin/alpha-actin ratio also increased at 1-2 weeks of exposure to hypoxia. Absolute contractility of the pulmonary arterial ring continuously decreased during hypoxia, whereas the basal active tonus of the pulmonary artery increased at 1-3 weeks. Nicardipine, the ETA-receptor antagonis, CI-1034 and the rho-kinase inhibitor Y27632 partially inhibited the elevated active tonus. Endothelin-1 content in the pulmonary hypertensive lung was continuously increased during exposure to hypoxia. In conclusion, the hypoxia-induced proliferative activity of PASMCs comprised a transient phase followed by a sustained phase. The change in PASMCs from a contractile to a synthetic phenotype also correlated with proliferative activity, which subsequently decreased PASMC contractility. The continuous production of endothelin-1 upon hypoxic exposure might contribute to the increased basal tonus of the pulmonary arterial wall, which might subsequently increase pulmonic arterial pressure, resulting in accelerated pulmonary hypertension.

KI fragen

Bookmark

View Full Paper