Premium
O2 sensing and Ca2+ release in hypoxic pulmonary vasoconstriction in non‐preconstricted pulmonary arteries from rats
Author(s) -
Aaronson Philip Irving,
Connolly Michelle Judith,
Prieto-Lloret Jesus,
Ward Jeremy P.T.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.871.6
Subject(s) - hypoxic pulmonary vasoconstriction , chemistry , vasoconstriction , superoxide dismutase , ryanodine receptor , medicine , pharmacology , endocrinology , biochemistry , oxidative stress , receptor
We assessed the roles of Ca 2+ release, the electron transport chain and NOX in hypoxic pulmonary vasoconstriction (HPV), the process by which hypoxia constricts pulmonary arteries (PA). HPV in the absence of pretone in 2 nd and 3 rd order rat PA branches gassed with 95% N 2 , 5% CO 2 for 40 min demonstrated an initial transient tension increase (phase 1) followed by a slow rise in tension (phase 2). Phase 1 was abolished but phase 2 was unaffected by the complex I inhibitor rotenone (1 μM). Both phases of HPV were abolished by the complex IV inhibitor cyanide (10 μM). Pretreatment of PA with superoxide dismutase (200 units/ml), catalase (200 units/ml), their combination, or with the putative NOX inhibitor VAS 2870 (10 μM) had no effect on either phase of HPV. The superoxide scavenger TEMPOL (3mM) reduced phase 1 by 42% and abolished phase 2. 10 μM NED‐19 had no effect on either phase of HPV. The PKC blocker Gö6983 (3 μM) reduced both phases by ~30%. Pretreatment with 100 μM ryanodine reduced both phases 1 by ~70%. Pretreatment with a combination of ryanodine (10 μM) and caffeine (10 mM) to deplete SR Ca 2+ abolished both phases. Applying zero Ca 2+ ‐PSS ablated phase 1 HPV but had no effect on phase 2, and re‐adding Ca 2+ during phase 2 did not increase contraction. These data indicate that O 2 sensing mechanisms for phase 1 and 2 differ, but in neither case involve NOX. Phase 2 HPV is apparently fully accounted for by the release of Ca 2+ from the SR.