Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

TY - JOUR

T1 - Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

AU - Robertson, T P

AU - Aaronson, P I

AU - Ward, J P T

PY - 2003/6/1

Y1 - 2003/6/1

N2 - 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 F-2alpha, 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.

AB - 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 F-2alpha, 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.

UR - http://www.scopus.com/inward/record.url?scp=0038172575&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00422.2002

DO - 10.1152/ajplung.00422.2002

M3 - Article

VL - 284

SP - L1121 - L1126

JO - AMERICAN JOURNAL OF PHYSIOLOGY: LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

JF - AMERICAN JOURNAL OF PHYSIOLOGY: LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

IS - 6

ER -