Lung Endothelial Dysfunction in Congestive Heart Failure Role of Impaired Ca2+ Signaling and Cytoskeletal Reorganization

Rationale: Congestive heart failure (CHF) frequently results in remodeling and increased tone of pulmonary resistance vessels. This adaptive response, which aggravates pulmonary hypertension and thus, promotes right ventricular failure, has been attributed to lung endothelial dysfunction. Objective: We applied real-time fluorescence imaging to identify endothelial dysfunction and underlying molecular mechanisms in an experimental model of CHF induced by supracoronary aortic banding in rats. Methods and Results: Endothelial dysfunction was evident in lungs of CHF rats as impaired endothelium-dependent vasodilation and lack of endothelial NO synthesis in response to mechanical stress, acetylcholine, or histamine. This effect was not attributable to downregulation of endothelial NO synthase. Imaging of the cytosolic Ca2+ concentration ([Ca2+]i) revealed a singular impairment of endothelial [Ca2+]i homeostasis and signaling characterized by a lack of [Ca2+]i oscillations and deficient or attenuated [Ca2+]i re...