title: Enhanced gene expression of renin-angiotensin system, TGF-beta1, endothelin-1 and nitric oxide synthase in right-ventricular hypertrophy.
abstract: It has been suggested that various vasoactive substances and growth factors are involved in left-ventricular myocardial hypertrophy and failure. However, limited data are available on the role of humoral factors involved in right-ventricular (RV) hypertrophy. To examine implications of humoral factors involved in the development of RV hypertrophy, altered mRNA expressions of the renin-angiotensin system (RAS), transforming growth factor (TGF)- beta1, endothelin-1 and nitric oxide synthase (NOS) were investigated in monocrotaline (MCT)-induced pulmonary hypertensive rats. Male Sprague-Dawley rats were treated with MCT (60 mg x kg(-1), s.c.) to induce a selective RV hypertrophy. Three or 6 weeks later, the heart was removed to determine the tissue gene expressions in the right and left ventricles (LV) by reverse transcription-polymerase chain reaction due to the relatively low mRNA expression levels of the RAS components in the ventricle (n= 6 in each group). MCT-treated rats showed a selective RV hypertrophy at weeks 3 and 6 of MCT treatment (the ratios of RV/body weight were 1.5- and 2.2-fold higher than the controls, respectively). Levels of renin and angiotensinogen mRNAs in the hypertrophied RV were significantly increased at both weeks 3 and 6 of MCT treatment. The angiotensin-converting enzyme mRNA level also increased approximately 2-fold at week 3. In contrast, RAS component mRNAs in the LV were not significantly altered by MCT treatment, except for a 1.8-fold increase of angiotensinogen mRNA at week 3. The expression of Ang II receptors, either AT1A or AT1B, was not significantly altered by MCT treatment. Furthermore, MCT treatment significantly increased TGF- beta1 mRNA levels in the RV at weeks 3 and 6, while it did not significantly affect them in the LV. Endothelin-1 mRNA expression was significantly higher in the RV at week 3, but was normalized at week 6 of MCT treatment. The gene expression of the endothelial constitutive isoform of NOS was increased in the RV at weeks 3 and 6, but not in the LV. Elevated gene expression of local RAS, along with TGF- beta1 and endothelin-1 in the present study may contribute to the development of RV hypertrophy. On the contrary, an enhanced ecNOS expression may be a mechanism counteracting the hypertrophy.
authors.affiliation: Department of Physiology, School of Medicine, Kyungpook University, Taegu, 700-422, Korea.
authors.forename: H K
authors.initials: HK
authors.lastname: Park
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.forename: C S
authors.initials: CS
authors.lastname: Kim
authors.forename: Y W
authors.initials: YW
authors.lastname: Paek
authors.forename: J U
authors.initials: JU
authors.lastname: Lee
authors.forename: W J
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics*; D015870:Gene Expression; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D019001:Nitric Oxide Synthase / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
chemical_list: D019332:Endothelin-1; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016686:Monocrotaline; D019001:Nitric Oxide Synthase