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

Calcium-sensitive potassium (K-Ca) channels play a critical role in mediati ng perinatal pulmonary vasodilation. Because infants with persistent pulmon ary hypertension of the newborn (PPHN) have blunted vasodilator responses t o birth-related stimuli, we hypothesized that lung K-Ca channel gene expres sion is decreased in PPHN. To test this hypothesis, we measured K-Ca channe l gene expression in distal lung homogenates from both fetal lambs with sev ere pulmonary hypertension caused by prolonged compression of the ductus ar teriosus 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, wi th lung 18S rRNA content as an internal control. Compared to that in contro l 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 uncha nged. 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.