OBJECTIVESTo investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms.

METHODSThirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups (8 in each group): model group (placebo), positive control group (27 mg/kg of Captopril Tablets), Sapindus saponins groups (27 mg/kg and 108 mg/kg, respectively). Another 8 healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter (BP-6). Furthermore, the contents of angiotensin II (Ang II) in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA), the gene expression of receptor angiotensin type 1 (AT1R) in aorta was determined by quantitative realtime polymerase chain reaction (qRT-PCR). The protein expression of transforming growth factor-β1 (TGF-β1) and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) was determined by Western blotting. The contents of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin (HE) or Masson staining.

RESULTSThirty minutes after single or continuous treatment, systolic blood pressure (SBP) was reduced significantly in Sapindus saponins groups. And the contents of AngII, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF-β1 were significantly suppressed dose-dependently (P<0.05 or P<0.01). With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly.

CONCLUSIONSOur findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang II and AT1R.

Angiotensin II ; metabolism ; Animals ; Aorta ; drug effects ; pathology ; physiopathology ; Blood Pressure ; drug effects ; Collagen ; metabolism ; Female ; Hypertension ; blood ; drug therapy ; enzymology ; physiopathology ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Phosphorylation ; drug effects ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Inbred SHR ; Receptor, Angiotensin, Type 1 ; metabolism ; Renin-Angiotensin System ; drug effects ; Sapindus ; chemistry ; Saponins ; pharmacology ; therapeutic use ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the effect of panax notoginseng saponins (PNS) injection on pulmonary artery pressure and the expression of p38MAPK in lung tissue of rats subjected to chronic hypoxia.

METHODSThirty adult male Sprague Dawley rats were randomly divided into three groups (ten in each group): rats in control group were exposed to normoxic condition and the rats in hypoxia group and PNS group were subjected to 4-week hypoxia, and PNS injection (50 mg · kg(-1) · d(-1)) was administrated intraperitoneally at 30 min in the PNS group daily before the rats were kept in the hypoxic chamber, while rats in the other two groups received equal dose of normal saline instead. After chronic hypoxia, mean pulmonary artery pressure (mPAP) and mean carotid artery pressure (mCAP) were measured. The heart and lung tissues were harvested, and right ventricle (RV) and left ventricle plus ventricular septum (LV+S) were weighed to calculate the ratio of RV/(LV+S). The expression of p38MAPK mRNA was determined by reverse transcription-polymerase chain reaction, the quantity of phosphorylated p38MAPK (p-p38MAPK) in rat lung tissues and pulmonary arterioles was determined by Western blot and immunohistochemistry.

RESULTSCompared with the control group, mPAP and the ratio of RV/(LV+S) in the hypoxia group were increased, the expression of p-p38MAPK in pulmonary arterioles and p38MAPK mRNA in the lung were higher (P<0.05). The changes of these parameters in the hypoxia group were significantly attenuated by PNS treatment (P<0.05).

CONCLUSIONPNS injection was shown to prevent hypoxic pulmonary hypertension at least partly by regulating p38MAPK pathway.

Animals ; Arterioles ; drug effects ; metabolism ; Blood Pressure ; drug effects ; Blotting, Western ; Carotid Arteries ; drug effects ; physiopathology ; Disease Models, Animal ; Heart Ventricles ; drug effects ; physiopathology ; Hemodynamics ; drug effects ; Hypertension, Pulmonary ; complications ; enzymology ; physiopathology ; Hypoxia ; complications ; enzymology ; physiopathology ; Injections ; Lung ; drug effects ; enzymology ; pathology ; physiopathology ; MAP Kinase Signaling System ; drug effects ; Male ; Panax notoginseng ; chemistry ; Pulmonary Artery ; drug effects ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

OBJECTIVETo observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH).

METHODTotally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot.

RESULTAfter the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC.

CONCLUSIONSesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.

Animals ; Dioxoles ; administration & dosage ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypertension, Pulmonary ; drug therapy ; enzymology ; genetics ; physiopathology ; Lignans ; administration & dosage ; Lung ; blood supply ; enzymology ; metabolism ; Male ; Membrane Glycoproteins ; genetics ; metabolism ; Monocrotaline ; adverse effects ; NADPH Oxidase 2 ; NADPH Oxidase 4 ; NADPH Oxidases ; genetics ; metabolism ; Pulmonary Artery ; drug effects ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Vascular Remodeling ; drug effects

OBJECTIVETo assess the association of plasma homocysteine (Hcy) level and 66A/G and 524C/T polymorphisms of methionine synthase reductase (MSR) gene with essential hypertension (EH) in ethnic Uygurs and Hans from Xinjiang.

METHODSFrom September 2011 to July 2014, 199 Uyghur and 216 Han patients were collected, while 195 healthy Uyghur ethnics and 217 healthy Han ethnics were recruited as the controls. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RELP) was adopted to detect the above polymorphisms. Enzyme immunological assay was applied to measure the levels of plasma Hcy.

RESULTSCompared with the control, plasma Hcy levels were significantly higher in EH group in both Uyghur and Han ethnics (P<0.05). In both ethnic groups, there were also significant differences in MSR 524C/T polymorphism between the patients and controls (Uyghur: chi-square=6.559, P=0.038; Han: chi-square=12.684, P=0.002). No significant difference was found in MSR 66A/G polymorphism between the patients and controls in both ethnic groups (P>0.05). Plasma Hcy level in those with a 66G/524C genotype was statistically higher than that with 66A/524T (P<0.05). After adjusting confounding factors such as gender and age, Logistic regression analysis indicated that age (OR=1.924, 95% CI:1.177- 3.164, P=0.009), obesity (OR=2.491, 95% CI: 1.584-3.920, P<0.01), hyperhomocysteine (OR=1.609, 95% CI: 1.016-2.548, P=0.043) were independent risk factors for EH in Uygurs, while age (OR=1.133, 95% CI: 1.010-81.272, P=0.033), hyperhomocysteine level (OR=3.894, 95% CI: 2.432-6.237, P<0.01), and obesity (OR=1.864, 95% CI: 1.141-3.046, P=0.013) were independent risk factors for EH in Han ethnics. No association was found between the polymorphisms and EH in Uygurs and Hans.

CONCLUSIONAge, hyperhomocysteine and obesity were common independent risk factors for EH in both Uygur and Han ethnics from Xinjiang. The MSR 66G genotype can increase the plasma concentration of Hcy, while MSR 524T genotype may reduce it. MSR 524C/T TT genotype may be a protective factor for EH. MSR polymorphisms 66A/G and 524C/T are not independent risk factors for EH in Uygur and Han ethnics from Xinjiang.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Essential Hypertension ; Female ; Ferredoxin-NADP Reductase ; genetics ; metabolism ; Homocysteine ; blood ; Humans ; Hypertension ; blood ; enzymology ; ethnology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) in the corpus cavernosum of spontaneous hypertensive rats (SHR) and their relationship with erectile dysfunction.

METHODSThis study included 10 male SHRs and 10 healthy male Wistar-Kyoto (WKY) rats as controls, all aged 12 weeks. We applied a series of electric stimuli to the major pelvic ganglions of the rats, observed changes in the ratio of intracavernosal to mean arterial blood pressure (ICP/MAP), measured the levels of serum testosterone (T) and endogenous H2S, and determined the expressions of CSE and CBS in the corpus cavernosum by Western blot and immunohistochemistry.

RESULTSNo obvious difference was found in the serum T level between the two groups. Compared with the WKY rats, the SHRs showed significant reduction in the ICP/MAP ratio, the contents of plasma H2S ([21.92 +/- 2.75] micromol/L vs [10.49 +/- 1.35] micromol/L, P < 0.05) and endogenous corpus cavernosal H2S ([87.67 +/- 2.12] nmol/mg prot vs [52.60 +/- 3.44] nmol/mg prot, P < 0.05), the level of endogenous H2S synthesis ([4.35 +/- 0.32] nmol/mg per min vs [1.14 +/- 0.07] nmol/mg per min, P < 0.05) and the expressions of CBS and CSE (P < 0.05). Immunohistochemistry showed that CSE and CBS were distributed mainly in the smooth muscle cells and vascular endothelial cells of the corpus cavernosum. The ICP/MAP ratio was highly positively correlated with the expressions of CSE (r = 0.977, P < 0.05) and CBS (r = 0.955, P < 0.05) in the corpus cavernosal tissue.

CONCLUSIONHypertension inhibits endogenous H2S synthesis by suppressing the expressions of CSE and CBS in the corpus cavernosum, which might be related with hypertension-induced reduction of erectile function.

Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Gene Expression Regulation ; Hydrogen Sulfide ; blood ; Hypertension ; metabolism ; Male ; Penis ; enzymology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

We evaluated the gender differences in the relation of baseline serum gamma-glutamyltransferase (GGT) levels to blood pressure (BP) change during 4 yr. 4,025 normotensive subjects (1,945 men and 2,080 women) who aged 40-69 yr at baseline participated in the Ansung-Ansan cohort of the Korean Genome Epidemiology Study were included. The associations of GGT with baseline BP or 4-yr change of BP were evaluated. GGT levels were associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline after adjusting for age, body mass index (BMI), HDL-cholesterol, triglyceride, C-reactive protein (CRP), current smoking status and alcohol intake (SBP, beta=1.28, P<0.001; DBP, beta=1.41, P<0.001). GGT levels were also associated with 4-yr change in BP after adjusting for age, BMI, HDL-cholesterol, triglyceride, CRP, current smoking status, alcohol intake and SBP (SBP, beta=1.08, P=0.001; DBP, beta=0.64, P=0.003). This association was statistically significant in men (SBP, beta=1.82, P<0.001; DBP, beta=1.05, P=0.001), but not in women (SBP, beta=0.38, P=0.466; DBP, beta=-0.37, P=0.304). Remarkably, this association between GGT and BP was significant in men at 40-49 yr of age. In summary, we found positive associations between GGT levels at baseline and the change of BP. The relation of GGT level and the change of BP was only significant in men, not in women, which warrants further studies to elucidate the biologic mechanisms.
Adult ; Aged ; Alcohol Drinking ; Blood Pressure/genetics ; C-Reactive Protein/analysis ; Cohort Studies ; Female ; Humans ; Hypertension/*enzymology/genetics ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Sex Factors ; Triglycerides/blood ; gamma-Glutamyltransferase/*blood/genetics

BACKGROUNDHypoxic pulmonary hypertension (HPH) contributes to the pathogenesis of cardiopulmonary diseases. Several lines of evidence indicate that the Rho A/Rho-kinase pathway play an important role in the progress of pulmonary hypertension. Stains have been shown exert numerous biological effects that are independent of their cholesterol-lowering property. We hypothesized that the Rho A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH rat model.

METHODSThirty-two Wistar rats were randomly divided into four groups: control group, hypoxic group, atovastatin group, and normal saline group. The control group was kept in a normoxia environment. The other groups were exposed to hypoxia for three weeks. Atovastatin was administered daily via a gastric gavage in the atovastatin group. We measured the mean pulmonary arterial pressure (mPAP), the ratio of the right ventricular weight to the sum of the weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall thickness/vascular external diameter (WT%), vascular area/total vascular area (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-κB activation in pulmonary vascular smooth muscle cells.

RESULTSCompared with the control group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P < 0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF-κB activation were all positive.

CONCLUSIONSThe Rho A/Rho-kinase pathway plays an important role in the development of HPH. Atorvastatin reversed HPH by inhibiting the activity of Rho A/Rho-kinase and NF-κB.

Animals ; Atorvastatin Calcium ; Blotting, Western ; Heptanoic Acids ; therapeutic use ; Hypertension, Pulmonary ; drug therapy ; enzymology ; Hypoxia ; metabolism ; Male ; NF-kappa B ; metabolism ; Pyrroles ; therapeutic use ; Random Allocation ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; rho-Associated Kinases ; metabolism ; rhoA GTP-Binding Protein ; metabolism

OBJECTIVETo study the roles of type II 11β-hydroxysteroid dehydrogenase (11β-HSD2) and it's signaling factors in the lung tissue in pathogenesis of persistent pulmonary hypertension (PPH) in neonatal rats.

METHODSSix Sprague-Dawley rats on the 19th day of pregnancy were randomly divided into PPH and control groups (n=3 each). The PPH group was intraperitoneally injected with indomethacin (0.5 mg/kg) twice daily and exposed in 12% oxygen for three days, in order to prepare a fetal rat model of PPH. The control group was intraperitoneally injected with an equal volume of normal saline and exposed to air. Neonatal rats were born by caesarean section from both groups on the 22nd day of pregnancy. In each group, 15 neonatal rats were randomly selected and sacrificed. 11β-HSD2 expression in the lung tissue of neonatal rats were observed by Confocal laser technology, and serum cortisol levels and prostacyclin, renin, angiotensin and aldosterone in the lung tissue of both groups were measured using ELISA.

RESULTS11β-HSD2 protein was widely expressed in the lung tissue of the control and PPH groups. The levels of 11β-HSD2 and prostacyclin in the lung tissue were lower in the PPH group than in the control group, while serum cortisol levels and renin, angiotensin and aldosterone in the lung tissue were higher in the PPH group than in the control group (P<0.05).

CONCLUSIONS11β-HSD2 and it's signaling factors play roles in pathogenesis of PPH in neonatal rats.

11-beta-Hydroxysteroid Dehydrogenase Type 2 ; analysis ; physiology ; Animals ; Animals, Newborn ; Female ; Hypertension, Pulmonary ; enzymology ; etiology ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

OBJECTIVETo observe the effects of up- or down-regulation of haemoxygenase 1 (HO-1) gene expression on intestinal mucosa injury induced by intra-abdominal hypertension (IAH).

METHODS(1) Reproduction of rat model of up- or down-regulation of HO-1 gene expression. Twenty-four healthy adult Wistar rats were divided into Co-PP (HO-1 specific revulsive) 2.5 mg, Co-PP 5.0 mg, Sn-PP (HO-1 specific inhibitor) 2.5 mg, and control groups according to the random number table, with six rats in each group. Rats in groups Co-PP 2.5 mg and Sn-PP 2.5 mg were respectively given Co-PP 2.5 mg/kg and Sn-PP 2.5 mg/kg by intraperitoneal injection, once every 12 hours for 3 days. The rats in group Co-PP 5.0 mg were intraperitoneally injected with Co-PP 5.0 mg/kg, once a day for 3 days. The rats in control group were treated with equal volume of normal saline by intraperitoneal injection. All rats were sacrificed on post injection day (PID) 4, and intestinal mucosa tissues were collected for determination of HO-1 mRNA expression. Optimal dose of Co-PP was chosen for the following experiment. (2) The influence of up- or down-regulation of HO-1 gene expression on intestinal mucosa injury under IAH condition. Another 24 healthy adult Wistar rats were divided into control, IAH, Co-PP+IAH, and Sn-PP+IAH groups according to the random number table, with six rats in each group. The rats in groups Co-PP+IAH and Sn-PP+IAH were intraperitoneally injected with 2.5 mg/kg Co-PP and 2.5 mg/kg Sn-PP, once every 12 hours for 3 days. Equal volume of normal saline was intraperitoneally injected into the rats in control group, once every 12 hours for 3 days. Then, nitrogen gas pneumoperitoneum was used to establish the model of IAH in rats of the latter three groups on PID 4, with IAP at 20 mm Hg (1 mm Hg = 0.133 kPa) , and it was maintained for 2 hours. Puncture and intubation were performed in rats of control group without inflating nitrogen gas. Jejunal segment in the length of 10-15 cm was harvested for collecting intestinal mucosa tissues to determine the HO-1 mRNA expression and diamine oxidase (DAO) content. Serum obtained from portal vein blood was collected to determine the D-lactate, TNF-α, and IL-6 contents. Another jejunal segment in the length of 1-2 cm was harvested for histopathological examination. Data were processed with one-way analysis of variance and t test.

RESULTS(1) The HO-1 mRNA expression in group Co-PP 2.5 mg was significantly higher than that in control and Co-PP 5.0 mg groups (with t values respectively 4.756, 3.175, P < 0.05 or P < 0.01). The HO-1 mRNA expression in group Sn-PP 2.5 mg was significantly lower than that in control group (t = 4.880, P < 0.01). The optimal dose of Co-PP for the following experiment was 2.5 mg/kg. (2) HO-1 mRNA expression in group Co-PP+IAH was 60 ± 5, and it was obviously higher than that of group IAH (49 ± 5, t = 3.811, P < 0.01) and control group (39 ± 4, t = 8.034, P < .001) . HO-1 mRNA expression was higher in group IAH than in control group (t = 3.826, P < 0.01). HO-1 mRNA expression in group Sn-PP+IAH was 29 ± 4, which was obviously lower than that of control group (t = 4.330, P < 0.01). The contents of DAO and D-lactate in group Co-PP+IAH were (0.52 ± 0.05) U/mL and (1.9 ± 0.6) mg/L, which were significantly lower than those in group IAH [(0.88 ± 0.06) U/mL and (4.3 ± 0.7) mg/L, with t values respectively 11.291, 6.376, P values all below 0.01], but still higher than those in control group [(0.34 ± 0.04) U/mL, (1.2 ± 0.5) mg/L, with t values respectively 6.886, 2.295, P < 0.05 or P < 0.01]. The contents of TNF-α and IL-6 were much lower in group Co-PP+IAH than in group IAH, but still higher than in control group (with t values from 3.781 to 18.557, P values all below 0.01). The contents of DAO, D-lactate, TNF-α, and IL-6 in group Sn-PP+IAH were all higher than those in the other 3 groups (with t values from 4.181 to 32.938, P values all below 0.01). Structure of epithelial cells from intestinal mucosa was intact and regularly arranged in rats of control group. Intestinal mucosal tissue was edematous, and the top of villi was anabrotic and necrotic in rats of group IAH. Compared with that of group IAH, the degree of intestinal mucosa injury was alleviated in rats of group Co-PP+IAH, while the pathology was aggravated in rats of group Sn-PP+IAH.

CONCLUSIONSUp-regulation of HO-1 gene expression can ameliorate intestinal mucosa injury caused by IAH, thus protecting intestinal mucosa tissues.

Animals ; Disease Models, Animal ; Gene Expression Regulation ; Heme Oxygenase (Decyclizing) ; metabolism ; Intestinal Mucosa ; enzymology ; pathology ; Intra-Abdominal Hypertension ; enzymology ; pathology ; Rats ; Rats, Wistar ; Up-Regulation

The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ETA) were significantly decreased in the shRNA group in week 4. The protein levels of ETA were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-alpha and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.
Animals ; Aspartic Acid Endopeptidases/*antagonists & inhibitors/blood/genetics ; Body Weight ; Heart Ventricles/physiopathology ; Hypertension, Pulmonary/chemically induced/*enzymology/mortality ; Lentivirus/genetics ; Lung/anatomy & histology/metabolism/pathology ; Male ; Metalloendopeptidases/*antagonists & inhibitors/blood/genetics ; Monocrotaline/toxicity ; Pulmonary Artery/drug effects/physiopathology ; RNA, Small Interfering/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin A/genetics/metabolism ; Survival Rate ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/metabolism