HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/L982    most recent 00361.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Becker, S. Articles by Aaronson, P. I. Search for Related Content PubMed PubMed Citation Articles by Becker, S. Articles by Aaronson, P. I.

Hypoxic pulmonary vasoconstriction in intact rat intrapulmonary arteries is not initiated by inhibition of Na⁺-Ca²⁺ exchange

Division of Asthma, Allergy, and Lung Biology, King's College London, London, United Kingdom

Submitted 14 September 2006 ; accepted in final form 3 July 2007

It has been proposed that a hypoxia-induced inhibition of the Na⁺-Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺]_i). In some experiments, fura pentakis(acetoxymethyl) ester-3 (fura PE-3) was also used to monitor [Ca²⁺]_i. HPV was elicited in IPA that were pretreated with 10 µM diltiazem and slightly preconstricted with PGF₂, which enhances the hypoxic response. Substitution of Na⁺ with Li⁺ increased HPV and the associated rise in [Ca²⁺]_i. Pretreatment with ouabain (100 µM) to diminish the Na⁺ gradient or with the reverse-mode NCX inhibitor KB-R7943 (3 or 10 µM) had no significant effect on HPV. Combined treatment with ouabain and low-[Na⁺] (24 mM) solution enhanced HPV strongly. The role of NCX in Ca²⁺ extrusion was examined by assessing the decrease in [Ca²⁺]_i in Ca²⁺-free physiological saline solution either containing or lacking Na⁺ following a high K⁺-induced loading of cellular [Ca²⁺]. Although the large initial rapid fall in [Ca²⁺] was Na⁺ independent, final recovery of [Ca²⁺] 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 Ca²⁺.

hypoxia; pulmonary artery