O2 sensing and Ca2+ release in hypoxic pulmonary vasoconstriction in non‐preconstricted pulmonary arteries from rats

Abstract

We assessed the roles of Ca2+ 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 2nd and 3rd order rat PA branches gassed with 95% N2, 5% CO2 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 Ca2+ abolished both phases. Applying zero Ca2+ ‐PSS ablated phase 1 HPV but had no effect on phase 2, and re‐adding Ca2+ during phase 2 did not increase contraction. These data indicate that O2 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 Ca2+ from the SR.