Chronic intrauterine pulmonary hypertension decreases calcium-sensitive potassium channel mRNA expression.
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.
Cornfield
D N
DN
Division of Pediatric Pulmonology and Critical Care Medicine, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. cornf001@tc.umn.edu
Resnik
E R
ER
Herron
J M
JM
Abman
S H
SH
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000196:embryology* / Q000235:genetics; D008168:Lung / Q000196:embryology*; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012756:Sheep
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated