Ca sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Robertson, Tom P., Philip I. Aaronson, and Jeremy P. T. Ward. Ca2 sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent. Am J Physiol Lung Cell Mol Physiol 284: L1121–L1126, 2003. First published February 28, 2003; 10.1152/ajplung.00422. 2002.—The main aim of this study was to determine the effects of endothelium removal on tension and intracellular Ca2 ([Ca2 ]i) during hypoxic pulmonary vasoconstriction (HPV) in rat isolated intrapulmonary arteries (IPA). Rat IPA and mesenteric arteries (MA) were mounted on myographs and loaded with the Ca2 -sensitive fluorophore fura PE-3. Arteries were precontracted with prostaglandin F2 , and the effects of hypoxia were examined. HPV in isolated IPA consisted of a transient constriction superimposed on a second sustained phase. Only the latter phase was abolished by endothelial denudation. However, removal of the endothelium had no effect on [Ca2 ]i at any point during HPV. The endothelin-1 antagonists BQ-123 and BQ-788 did not affect HPV, although constriction induced by 100 nM endothelin-1 was abolished. In MA, hypoxia induced an initial transient rise in tension and [Ca2 ]i, followed by vasodilatation and a fall in [Ca2 ]i to (but not below) prehypoxic levels. These results are consistent with sustained HPV being mediated by an endothelium-derived constrictor factor that is distinct from endothelin-1 and that elicits vasoconstriction via Ca2 sensitization.