title: The effects of debanding on the lung expression of ET-1, eNOS, and cGMP in rats with left ventricular pressure overload.
abstract: 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.
authors.affiliation: Department of Chest Surgery, Kaohsiung Medical University, Taiwan.
authors.forename: Shah-Hwa
authors.initials: SH
authors.lastname: Chou
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Jiunn-Ren
authors.initials: JR
authors.lastname: Wu
authors.forename: Mian-Shin
authors.initials: MS
authors.lastname: Tan
authors.forename: Chaw-Chi
authors.initials: CC
authors.lastname: Chiu
authors.forename: Ing-Jun
authors.initials: IJ
authors.lastname: Chen
authors.forename: Acro Y
authors.initials: AY
authors.lastname: Jeng
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Chang
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.forename: Zen-Kong
authors.initials: ZK
authors.lastname: Dai
mesh_terms: 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
chemical_list: D019332:Endothelin-1; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP