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

Adverse events during the perinatal period, like hypoxia, have been associated with adult diseases. In pulmonary vessels, K super(+) channels play an important role in the regulation of vascular tone. In the fetus, Ca super(2+)-activated K super(+) channels (K sub(Ca)) are predominant, whereas from birth voltage-gated K super(+) channels (K sub(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 super(+) channels in adulthood. We evaluated the effects of perinatal hypoxia on K sub(V) and K sub(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 sub(V) channels contributed to this current, whereas in mice born in hypoxia both K sub(V) and K sub(Ca) channels were implicated. K sub(V) channel activity was even higher in mice born in hypoxia than in controls. Therefore, perinatal hypoxia results in increased K sub(Ca) and K sub(V) channel activity in adult PA. Moreover, PA of adults born in hypoxia displayed higher large-conductance K sub(Ca) alpha -subunit and K sub(V)1.5 alpha -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 sub(Ca) channels and only slightly by K sub(V) channels, whereas following perinatal hypoxia both K sub(Ca) and K sub(V) channels contributed to this relaxation. Thus perinatal hypoxia results in altered expression and activity of different K super(+) channels in the adult main PA, which could contribute to modifications of pulmonary vasoreactivity.