Enhanced gene expression of renin–angiotensin system, TGF-β1, 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. 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)- β1, 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 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 AT1Aor AT1B, was not significantly altered by MCT treatment. Furthermore, MCT treatment significantly increased TGF-β1 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- β1and 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.