Hypoxic pulmonary vasoconstriction in intact rat intrapulmonary arteries is not initiated by inhibition of Na+-Ca2+ exchange.
It has been proposed that a hypoxia-induced inhibition of the Na(+)-Ca(2+) exchanger (NCX) contributes to hypoxic pulmonary vasoconstriction (HPV). By recording isometric tension development in rat intrapulmonary arteries (IPA), we examined the effect on HPV of maneuvers that reduce the ability of NCX to regulate intracellular Ca(2+) concentration ([Ca(2+)](i)). In some experiments, fura pentakis(acetoxymethyl) ester-3 (fura PE-3) was also used to monitor [Ca(2+)](i). HPV was elicited in IPA that were pretreated with 10 microM diltiazem and slightly preconstricted with PGF(2alpha), which enhances the hypoxic response. Substitution of Na(+) with Li(+) increased HPV and the associated rise in [Ca(2+)](i). Pretreatment with ouabain (100 microM) to diminish the Na(+) gradient or with the reverse-mode NCX inhibitor KB-R7943 (3 or 10 microM) had no significant effect on HPV. Combined treatment with ouabain and low-[Na(+)] (24 mM) solution enhanced HPV strongly. The role of NCX in Ca(2+) extrusion was examined by assessing the decrease in [Ca(2+)](i) in Ca(2+)-free physiological saline solution either containing or lacking Na(+) following a high K(+)-induced loading of cellular [Ca(2+)]. Although the large initial rapid fall in [Ca(2+)] was Na(+) independent, final recovery of [Ca(2+)] to its basal level was delayed in the absence of Na(+). Therefore, HPV persisted or was increased under conditions in which forward-mode NCX was already attenuated or prevented, demonstrating that inhibition of NCX by hypoxia is unlikely to initiate HPV. Instead, NCX appears to act to inhibit HPV as would be expected if it is functioning to extrude Ca(2+).
Becker
Silke
S
Division of Asthma, Allergy, and Lung Biology, King's College London, London, United Kingdom.
Moir
Lyn M
LM
Snetkov
Vladimir A
VA
Aaronson
Philip I
PI
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D007537:Isometric Contraction; D008094:Lithium / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D019831:Sodium-Calcium Exchanger; D008094:Lithium; D012964:Sodium; D011188:Potassium; D002118:Calcium