Elevated pulmonary pressure and right ventricular (RV) dysfunction are the hallmarks of pulmonary vascular disease in animal models and human patients with pulmonary arterial hypertension (PAH). Monocrotaline models of PAH are widely used to study the pathophysiology of PAH. The purpose of this study was to evaluate the severity of PAH rat model by tissue Doppler imaging (TDI).

PAH was induced in Sprague-Dawley rats by monocrotaline (M) group. The peak systolic (s'), early diastolic (e'), and late diastolic myocardial velocities (a') were measured using TDI at basal segments. Tricuspid annular plane systolic excursion (TAPSE) was measured in the 4-chamber view. Velocity of a tricuspid regurgitation (TR) jet was measured to estimate the pulmonary artery pressure to assess the severity of PAH.

Decrease in the RV shortening fraction and ejection fraction were observed in the M group compared with the control (C) group. RV e' velocity and s' velocity were significantly lower in the M group compared with the C group. The TAPSE was significantly lower in the M group compared with the C group (1.26±0.22 mm vs. 2.83±0.34 mm). The TR velocity was significantly higher in the M group compared with the C group (4.48±0.34 m/sec vs. 1.23±0.02 m/sec).

TAPSE is an easily obtainable, widely recognized and clinically useful echocardiographic parameter of global RV function in the PAH rat model. We recommend that TDI would be a helpful diagnostic tool to evaluate the RV function in PAH rat model.

Simvastatin has been reported to attenuate the development of pulmonary hypertension through increased apoptosis as well as reduced proliferation of smooth muscle cells in obstructive vascular lesions. Microarray experiment can accomplish many genetic tests in parallel. The purpose of this study is to evaluate altered expressions of gene in rat hearts with monocrotaline (MCT)-induced pulmonary arterial hypertension after simvastatin treatment.

Six-week-old male rats were grouped as follows: control group (C group, saline injection), M group (MCT 60 mg/kg), and S group (MCT 60 mg/kg plus 10 mg/kg/day simvastatin by gavage during 28 days). Body weight, right ventricular pressure and right ventricular/left ventricle+septum ratio in each group were measured. The rats were sacrificed after 28 days. Total RNA was extracted from the rat heart tissue and microarray analysis was performed.

Administration of simvastatin significantly inhibited the progression of right ventricular hypertrophy at day 28 in the S group than in the M group. Compared with the C group, MCT was associated with a significant difference in expression of genes related to biosynthesis and with the regulation of heart contraction rate. Simvastatin treatment resulted in a significantly changed expression of genes about the regulation of progression through cell cycle and system development compared to the M group. The expressions of nitric oxide synthase and brain natriuretic peptide were significantly decreased after simvastatin treatment.

Administration of simvastatin exerted inhibitory effects on right ventricular hypertrophy during the development of MCT-induced pulmonary arterial hypertension in rats. Simvastatin changes the expression of genes associated with various functions.

Spontaneously hypertensive rats (SHR) are frequently used as rat models of essential hypertension. The mechanism for the development of hypertension is complicated and it is unknown. The renin-angiotensin system (RAS) plays a key role in the control of blood pressure. Microarrays are a powerful tool for studying genetics. The purpose of this study was to investigate changes of gene expression in the heart tissues of SHR after losartan treatment to provide basic data that is useful in the early diagnosis of hypertension and gene treatment.

Rats were divided into three groups: the control (C) group; the hypertension (H) group (SHR), and the losartan (L) group; treated with losartan (10 mg/kg/day) in SHR. Rats were sacrificed at week 5 and microarray analysis was performed.

102 gene expressions including the genes associated with cell proliferation such as Raf1, Uchl1, Btla, Spock1 were increased. The other 139 gene expressions, including the genes related to the regulation of metabolism such as TFIID, Auf1, Bmp, Hub, Taf51 showed decreases in gene expression. A total of 31 genes were differentially expressed in the L group compared to the H group. Of these, 16 genes including the genes associated with macromolecule metabolism such as MGC105766, Ppp1r1a, Rpl3l showed increased expression. The other 15 genes including the genes associated with primary metabolism such as Mcpt4, Ngn3, Tdo, Ak2 Hyal2 showed decreased expressions.

According to microarray analysis, there was significant gene expression change in SHR compared with normal rats as well as significant gene expression changes after losartan treatment in SHR.