The effects of chronic hypoxia on pulmonary vascular reactivity in mice genetically deficient in connexin 43

Background: Pulmonary hypertension is characterized by abnormal vasoconstriction and vascular remodelling. Cellular communications via gap junctions are important for control and coordination of vascular function. Connexin 43 (Cx43) is the predominant gap junction forming transmembrane protein in the vasculature. Recent evidence suggests that connexin mediated signalling plays a role in pulmonary vascular function. The aim of this study was to investigate the effects of chronic hypoxia on pulmonary vascular reactivity in Cx43 heterozygous (Cx43 +/- ) mice. Methods: Wildtype (WT) and Cx43 +/- male mice (C57BL6, 7-9 months old) were exposed to two weeks of hypobaric hypoxia (550mbar), while control littermates were kept in normoxic conditions. Mice were culled and intra-lobar pulmonary arteries dissected free and mounted on a wire myograph. Cumulative concentration response curves to endothelin-1 (ET-1) and serotonin were constructed. Gene expression in main and branch pulmonary arteries (PAs) was analysed by qRT PCR. Results: Under normoxic conditions, ET-1 showed increased potency in Cx43 +/- mice (P max ) was significantly greater in Cx43 +/- mice than WT mice (P +/- mice under either normoxic or hypoxic conditions. Cx43 mRNA expression was significantly (P +/- mice during hypoxia. Conclusion: Cx43 +/- mice show dysfunctional pulmonary vascular reactivity under both normoxic and chronic hypoxic conditions.