Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension.
Nitric oxide (NO), produced by endothelial (e) NO synthase (NOS), is critically involved in the cardiopulmonary transition from fetal to neonatal life. We have previously shown that NO-dependent relaxation is attenuated in intrapulmonary arteries from fetal lambs with pulmonary hypertension (PHT) created by prenatal ligation of the ductus arteriosus. In the present study, we determined whether this is due to altered pulmonary eNOS expression. eNOS and neuronal NOS (nNOS) protein expression were assessed in lungs from near-term control lambs and PHT lambs that underwent ductal ligation 10 days earlier. eNOS protein expression was decreased 49% in PHT lung. In contrast, nNOS protein abundance was unchanged. NOS enzymatic activity was also diminished in PHT vs. control lung (60 +/- 3 vs. 110 +/- 7 fmol.mg protein-1.min-1, respectively). Paralleling the declines in eNOS protein and NOS enzymatic activity, eNOS mRNA abundance was decreased 64% in PHT lung. Thus pulmonary eNOS gene expression is attenuated in the lamb model of fetal PHT. Because NO modulates both vasodilation and vascular smooth muscle growth, diminished eNOS expression may contribute to both the abnormal vasoreactivity and the excessive muscularization of the pulmonary circulation in fetal PHT.
Shaul
P W
PW
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235, USA.
Yuhanna
I S
IS
German
Z
Z
Chen
Z
Z
Steinhorn
R H
RH
Morin
F C
FC
D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000196:embryology* / Q000201:enzymology; D005260:Female; D005333:Fetus / Q000201:enzymology* / Q000502:physiology*; D015870:Gene Expression; D006976:Hypertension, Pulmonary / Q000196:embryology*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D011651:Pulmonary Artery / Q000196:embryology* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep / Q000196:embryology
D018076:DNA, Complementary; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase