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

²Neonatal Research Laboratory, Department of Pediatrics, University Hospital Center and University of Lausanne, Lausanne, Switzerland; and ¹Laboratory 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, Ca²⁺-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_V1.5 -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

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