Enhanced gene expression of renin-angiotensin system, TGF-ss(1), endothelin-1 and nitric oxide synthase in right-ventricular hypertrophy

It has been suggested that various vasoactive substances and growth factors are involved in left-ventricular myocardial hypertrophy and failure. Howev er, limited data are available on the role of humoral factors involved in r ight-ventricular (RV) hypertrophy. To examine implications of humoral facto rs involved in the development of RV hypertrophy, altered mRNA expressions of the renin-angiotensin system (RAS), transforming growth factor (TGF)-bet a (1). endothelin-1 and nitric oxide synthase (NOS) were investigated in mo nocrotaline (MCT)-induced pulmonary hypertensive rats. Male Sprague-Dawley rats were treated with MCT (60 mg kg(-1), s.c.) to induce a selective RV hy pertrophy. Three or 6 weeks later, the heart was removed to determine the t issue gene expressions in the right and left ventricles (LV) by reverse tra nscription-polymerase chain reaction due to the relatively low mRNA express ion levels of the RAS components in the ventricle (n = 6 in each group). MC T-treated rats showed a selective RV hypertrophy at weeks 3 and 6 of MCT tr eatment (the ratios of RV/body weight were 1.5- and 2.2-fold higher than th e 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 app roximately 2-fold at week 3, In contrast, RAS component mRNAs in the LV wer e not significantly altered by MCT treatment, except for a 1.8-fold increas e of angiotensinogen mRNA at week 3, The expression of Ang II receptors, ei ther AT(1A) or AT(1B), was not significantly altered by MCT treatment. Furt hermore, MCT treatment significantly increased TGF-beta (1) 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 t he 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 w ith TGF-beta (1) and endothelin-1 in the present study may contribute to th e development of RV hypertrophy. On the contrary, an enhanced ecNOS express ion may be a mechanism counteracting the hypertrophy. (C) 2001 Academic Pre ss.