Perinatal Hypoxia Enhances Cyclic Adenosine Monophosphate–mediated BKCa Channel Activation in Adult Murine Pulmonary Artery
Copyright policy )Perinatal Hypoxia Enhances Cyclic Adenosine Monophosphate–mediated BKCa Channel Activation in Adult Murine Pulmonary Artery
Exposure to perinatal hypoxia results in alteration of the adult pulmonary circulation, which is linked among others to alterations in K(+) channels in pulmonary artery (PA) smooth muscle cells. In particular, large conductance Ca(2+)-activated K(+) (BK(Ca)) channels protein expression and activity were increased in adult PA from mice born in hypoxia compared with controls. We evaluated long-term effects of perinatal hypoxia on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway-mediated activation of BK(Ca) channels, using isoproterenol, forskolin, and dibutyryl-cAMP. Whole-cell outward current was higher in pulmonary artery smooth muscle cells from mice born in hypoxia compared with controls. Spontaneous transient outward currents, representative of BK(Ca) activity, were present in a greater proportion in pulmonary artery smooth muscle cells of mice born in hypoxia than in controls. Agonists induced a greater relaxation in PA of mice born in hypoxia compared with controls, and BK(Ca) channels contributed more to the cAMP/PKA-mediated relaxation in case of perinatal hypoxia. In summary, perinatal hypoxia enhanced cAMP-mediated BK(Ca) channels activation in adult murine PA, suggesting that this pathway could be a potential target for modulating adult pulmonary vascular tone after perinatal hypoxia.
- University of Geneva Switzerland
- University Hospital of Lausanne Switzerland
- University of Lausanne Switzerland
Male, Colforsin, Age Factors, Isoproterenol, Pulmonary Artery, Muscle, Smooth, Vascular, Mice, Inbred C57BL, Mice, Pregnancy, Prenatal Exposure Delayed Effects, Cyclic AMP, Animals, Female, Hypoxia, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Male, Colforsin, Age Factors, Isoproterenol, Pulmonary Artery, Muscle, Smooth, Vascular, Mice, Inbred C57BL, Mice, Pregnancy, Prenatal Exposure Delayed Effects, Cyclic AMP, Animals, Female, Hypoxia, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
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