Differential changes in endothelin-1 and endothelial nitric oxide synthase gene expression in rats with a chronic high pulmonary flow.
The expressions of endothelin-1 (ET-1) and endothelial nitric oxide synthase were assessed in the lung of adult Wistar rats (n = 6/group) undergoing an abdominal aortocaval shunt to increase pulmonary blood flow for 4, 8 or 12 weeks. The shunt resulted in significant medial hypertrophy of the pulmonary artery without significant increases in pulmonary and systemic arterial pressure. A competitive reverse transcriptase-polymerase chain reaction demonstrated significant increases in pulmonary preproET-1 mRNA at 12 weeks (mean +/- standard error of the mean; shunt, 1.82 +/- 0.12; sham, 1.00 +/- 0.15; P < 0.05) and in pulmonary endothelial nitric oxide synthase mRNA at both 8 weeks (shunt, 1.57 +/- 0.12; sham, 1.00 +/- 0.18; P < 0.05) and 12 weeks (shunt, 1.89 +/- 0.18; sham, 1.00 +/- 0.13; P < 0.05). In addition, western blot analysis showed increases in pulmonary endothelial nitric oxide synthase protein by 126% and 164% at 8 and 12 weeks, respectively, in the shunt animals. However, the plasma ET-1 concentrations and the lung ET-1 contents were unchanged. These results indicate that endothelial nitric oxide synthase gene expression was upregulated, prior to that of ET-1, at the transcriptional level during pulmonary vascular remodeling in this chronic shunt model.
Dai
Zen-Kong
ZK
Division of Cardiology and Pulmonology, Department of Pediatrics, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tan
Mian-Shin
MS
Chai
Chee-Yin
CY
Chen
Ing-Jun
IJ
Jeng
Arco Y
AY
Kwan
Aij-Lie
AL
Howng
Sheng-Long
SL
Lu
Chu-Chong
CC
Wu
Jiunn-Ren
JR
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D001166:Arteriovenous Shunt, Surgical; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011651:Pulmonary Artery / Q000201:enzymology* / Q000503:physiopathology; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014158:Transcription, Genetic; D014684:Venae Cavae / Q000601:surgery
D019332:Endothelin-1; D011498:Protein Precursors; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat