Ca²⁺sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Abstract

The main aim of this study was to determine the effects of endothelium removal on tension and intracellular Ca 2+ ([Ca 2+ ] 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 Ca 2+ -sensitive fluorophore fura PE-3. Arteries were precontracted with prostaglandin F 2α , 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 [Ca 2+ ] 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 [Ca 2+ ] i , followed by vasodilatation and a fall in [Ca 2+ ] 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 Ca 2+ sensitization.