The effects of debanding on the lung expression of ET-1, eNOS, and cGMP in rats with left ventricular pressure overload.
Pulmonary hypertension (PH) usually develops secondary to left ventricular (LV) dysfunction; therefore, it is also called retrograde PH. To investigate our hypothesis that PH is at least partially reversible, as in some congenital heart diseases, in a rat model we investigated whether release of constriction could attenuate pulmonary vascular remodeling and change the expression of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS). We used rats with LV dysfunction produced by an ascending aortic banding. In this study, there were four groups enrolled: 4-weeks banded (AOB(1-28); n = 7), 7-weeks banded (AOB(1-49); n = 7), debanded groups (AOB(1-28)/DeB(29-49); n = 7), and rats receiving a sham operation (n = 7). Subsequently, there was significant attenuation of medial hypertrophy in pulmonary arterioles and reversal of PH in the AOB(1-28)/DeB(29-49) group (sham, 19 +/- 1.3 mm Hg; AOB(1-28), 31 +/- 2.7 mm Hg; AOB(1-49), 32 +/- 2.7 mm Hg; and AOB(1-28)/DeB(29-49), 20 +/- 1.3 mm Hg). PreproET-1 mRNA and eNOS mRNA were measured by competitive reverse transcriptase (RT) polymerase chain reaction (PCR), and eNOS was measured by Western blotting. Compared with the banded groups, debanding significantly decreased pulmonary preproET-1 mRNA, pulmonary ET-1 (sham, 210 +/- 12 pg/g protein; AOB(1-28), 242 +/- 12 pg/g protein; AOB(1-49), 370 +/- 49 pg/g protein; and AOB(1-28)/DeB(29-49), 206 +/- 1.9 pg/g protein), and plasma ET-1 levels (sham, 10.1 +/- 1.5 pg/ml; AOB(1-28), 13.4 +/- 2.0 pg/ml; AOB(1-49), 15.4 +/- 2.0 pg/ml; and AOB(1-28)/DeB(29-49), 10.3 +/- 0.9 pg/ml protein). Debanding could not, however, alter pulmonary eNOS, eNOS mRNA, or cGMP. These findings suggest that pulmonary vascular remodeling, increased pulmonary arterial pressure, and upregulation of ET-1 gene expression are all reversible. We infer that it is the upregulated gene expression of ET-1, not eNOS, that is closely related to the development of the PH secondary to 4 weeks of aortic banding.
Chou
Shah-Hwa
SH
Department of Chest Surgery, Kaohsiung Medical University, Taiwan.
Chai
Chee-Yin
CY
Wu
Jiunn-Ren
JR
Tan
Mian-Shin
MS
Chiu
Chaw-Chi
CC
Chen
Ing-Jun
IJ
Jeng
Acro Y
AY
Chang
Chung-I
CI
Kwan
Aij-Lie
AL
Dai
Zen-Kong
ZK
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D019332:Endothelin-1; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP