Effects of increased pulmonary flow on the expression of endothelial nitric oxide synthase and endothelin-1 in the rat.
The purpose of the study was to assess whether increased pulmonary flow and subsequent development of pulmonary vascular remodelling could alter the expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in the rat lung. Nine 42-day-old Wistar rats underwent abdominal aortocaval shunt to increase pulmonary blood flow for 12 weeks. The shunt resulted in significant medial hypertrophy of pulmonary artery without significant alterations in pulmonary or systemic blood pressure. Using competitive reverse transcription-PCR, significant increases in the preproET-1 mRNA expression and eNOS mRNA expression in the lungs of rats with abdominal aortocaval shunt were detected. Increased eNOS protein in the lung of shunt rats was also found by Western blot analysis. However, the plasma ET-1 concentration in the pulmonary artery (sham: 5+/-0.7 pg/ml; shunt: 6+/-0.8 pg/ml) or the lung ET-1 content (sham: 218+/-41 ng/g protein; shunt: 224+/-40 ng/g protein) was unchanged. There was an elevated immunohistochemical expression of eNOS, but not ET-1, in the pulmonary vascular endothelium in rats with the shunt. These results suggest that eNOS and ET-1 may be involved in remodelling prior to the development of pulmonary hypertension.
Division of Cardiology and Pulmonology, Department of Pediatrics, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Sun-Ming District, Kaohsiung, Taiwan.
Zen-Kong
ZK
Dai
Mian-Shin
MS
Tan
Chee-Yin
CY
Chai
Ing-Jun
IJ
Chen
Arco Y
AY
Jeng
Jiunn-Ren
JR
Wu
D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D016232:Endothelins / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D006984:Hypertrophy; D007150:Immunohistochemistry / Q000379:methods; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D011498:Protein Precursors / Q000235:genetics; D011651:Pulmonary Artery / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat