Differential change in expression of pulmonary ET-1 and eNOS in rats after chronic left ventricular pressure overload.
Pressure overload in the left ventricle of the heart follows a chronic and progressive course, resulting in eventual left heart failure and pulmonary hypertension (PH). The purpose of this research was to determine whether a differential pulmonary gene change of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS) occurred in adult rats with left ventricular overload. Eight groups of eight rats each were used (four rats with banding and four rats with sham operations). The rats underwent ascending aortic banding for 1 day, 2 weeks, 4 weeks, and 12 weeks before sacrifice. Significant medial hypertrophy of the pulmonary arterioles developed in two groups (4 and 12 weeks). Increased pulmonary arterial pressures were noted in three groups (1 day, 4 weeks, and 12 weeks). The aortic banding led to significant increases in pulmonary preproET-1 messenger RNA (mRNA) at 1 day and 12 weeks, and in pulmonary eNOS mRNA at 1 day and 12 weeks. In addition, there was increased pulmonary eNOS content at 1 day and 12 weeks in the banded rats, and increased lung cGMP levels were observed at 1 day. Increased lung ET-1 levels were also noted at 1 day (banded, 310 +/- 12 ng/g protein; sham, 201 +/- 12 ng/g protein; P < 0.01), 4 weeks (banded, 232 +/- 12 ng/g protein; sham, 201 +/- 12 ng/g protein; P < 0.01) and 12 weeks (banded, 242 +/- 12 ng/g protein; sham, 202 +/- 12 ng/g protein; P < 0.01). This indicates that the upregulated expression of ET-1 developed at least 4 weeks before eNOS expression in the course of PH, and, thus, medication against ET-1 could play a crucial role in treating PH with cardiac dysfunction secondary to aortic banding.
Tan
Mian-Shin
MS
Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Taiwan.
Chai
Chee-Yin
CY
Wu
Jiunn-Ren
JR
Yeh
Jwu-Lai
JL
Chen
Ing-Jun
IJ
Kwan
Aij-Lie
AL
Jeng
Arco Y
AY
Yang
Huey-Yu
HY
Lee
Meng-Hsun
MH
Dai
Zen-Kong
ZK
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology
D019332:Endothelin-1; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III