Upregulated neurohumoral factors are associated with left ventricular remodeling and poor prognosis in rats with monocrotaline-induced pulmonary arterial hypertension

作者：Usui Shin ichi; Yao Atsushi^*; Hatano Masaru; Kohmoto Osami; Takahashi Toshiyuki; Nagai Ryozo; Kinugawa Kichiro

来源：Circulation Journal, 2006, 70(9): 1208-1215.

DOI：10.1253/circj.70.1208

• carvedilol
• hypertrophy
• monocrotaline
• pulmonary arterial hypertension
• valsartan

Background Left ventricular remodeling might be involved in the pathophysiology of right ventricular hypertrophy/failure due to pulmonary arterial hypertension (PAH), while the left ventricle is considered not under pressure/volume overload.
Methods and Results Rats with monocrotaline-induced PAH were used in the present study to examine whether upregulated neurohumoral factors may induce left ventricular (LV) remodeling and (/or) contribute to prognosis. Morphological analysis revealed a significant increase in the weight of the free walls of both ventricles and the interventricular septum, indicating biventricular hypertrophy, although systemic blood pressure was not elevated. RNase protection assay demonstrated the activation of a fetal gene program in the cardiac muscle of the left and right ventricular free walls. Similar activation of the fetal gene program was observed in the LV of rats continuously infused with angiotensin (AT) It, although this was not the case for rats infused with isoproterenol. Measured plasma levels of ATII, noradrenaline, and brain natriuretic peptide (BNP) were all significantly elevated in the PAH rats. Furthermore, the plasma BNP level positively correlated with the ratio of heart weight to body weight and the plasma level of ATII. Not right but LV hypertrophy was significantly reduced by treatment with an AT H type I receptor blocker, valsartan, whereas the effect of an adrenergic alpha(1) and beta(1,2) blocker, carvedilol, was borderline. Survival rate in the PAH rats was significantly improved when they were treated with valsartan or carvedilol.
Conclusions Upregulated neurohumoral factors seem to play an important role in LV remodeling without mechanical overload, and are associated with impairment of prognosis in rats with PAH.

• 出版日期2006-9