Chronic intrauterine pulmonary hypertension decreases calcium-sensitive potassium channel mRNA expression

Abstract

Calcium-sensitive potassium (K Ca ) channels play a critical role in mediating perinatal pulmonary vasodilation. Because infants with persistent pulmonary hypertension of the newborn (PPHN) have blunted vasodilator responses to birth-related stimuli, we hypothesized that lung K Ca channel gene expression is decreased in PPHN. To test this hypothesis, we measured K Ca channel gene expression in distal lung homogenates from both fetal lambs with severe pulmonary hypertension caused by prolonged compression of the ductus arteriosus and age-matched, sham-operated animals (controls). After at least 9 days of compression of the ductus arteriosus, fetal lambs were killed. To determine lung K Ca channel mRNA levels, primers were designed against the known sequence of the K Ca channel and used in semiquantitative RT-PCR, with lung 18S rRNA content as an internal control. Compared to that in control lambs, lung K Ca channel mRNA content in the PPHN group was reduced by 26 ± 6% ( P < 0.02), whereas lung voltage-gated K + 2.1 mRNA content was unchanged. We conclude that lung K Ca channel mRNA expression is decreased in an ovine model of PPHN. Decreased K Ca channel gene expression may contribute to the abnormal pulmonary vascular reactivity associated with PPHN.