Perinatal hypoxia triggers alterations in K+ channels of adult pulmonary artery smooth muscle cells

2 Neonatal Research Laboratory, Department of Pediatrics, University Hospital Center and University of Lausanne, Lausanne, Switzerland; and 1 Laboratory of Vascular Cell Physiology, Department of Zoology, University of Geneva, Geneva, Switzerland Submitted 30 March 2007 ; accepted in final form 21 August 2007 Adverse events during the perinatal period, like hypoxia, have been associated with adult diseases. In pulmonary vessels, K + channels play an important role in the regulation of vascular tone. In the fetus, Ca 2+ -activated K + channels (K Ca ) are predominant, whereas from birth voltage-gated K + channels (K V ) prevail in the adult. We postulated that perinatal hypoxia could alter this maturational shift and influence regulation of pulmonary vascular tone in relation to K + channels in adulthood. We evaluated the effects of perinatal hypoxia on K V and K Ca channels in the adult main pulmonary artery (PA) using a murine model. Electrophysiological measurements showed a greater outward current in PA smooth muscle cells of mice born in hypoxia than in controls. In controls, only K V channels contributed to this current, whereas in mice born in hypoxia both K V and K Ca channels were implicated. K V channel activity was even higher in mice born in hypoxia than in controls. Therefore, perinatal hypoxia results in increased K Ca and K V channel activity in adult PA. Moreover, PA of adults born in hypoxia displayed higher large-conductance K Ca -subunit and K V 1.5 -subunit protein expression than controls. Interestingly, relaxation induced by nitric oxide (NO) donors [ S -nitroso- N -acetyl-D, L -penicillamine, 2-( N , N -diethylamino)-diazenolate-2-oxide] in isolated PA of control mice was not mediated by K Ca channels and only slightly by K V channels, whereas following perinatal hypoxia both K Ca and K V channels contributed to this relaxation. Thus perinatal hypoxia results in altered expression and activity of different K + channels in the adult main PA, which could contribute to modifications of pulmonary vasoreactivity. mouse; potassium ion channel activity; potassium ion channel blockers; nitric oxide donors Address for reprint requests and other correspondence: J. F. Tolsa, Neonatal Research Laboratory, Dept. of Pediatrics, 1011 Lausanne-CHUV, Switzerland (e-mail: Jean-Francois.Tolsa{at}chuv.ch )