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 effects of rapamycin (RAP) on pulmonary hypertension (PH) in rats, and to provide new insights into medication selection for the clinical treatment of PH.

METHODSFifty male Sprague-Dawley rats were randomly divided into blank control, PH model, solvent control, RAP 1, and RAP 2 groups. A rat model of PH was induced by left pneumonectomy (PE) and monocrotaline (MCT). At 5 days after PH model establishment, the solvent control group and the RAP 1 group received an intramuscular injection of solvent and RAP, respectively. At 35 days after PH model establishment, the RAP 2 group received an intramuscular injection of RAP. The mean pulmonary artery pressure (mPAP) and the right ventricle/left ventricle plus septum weight ratio (RV/LV+S) were measured in each group. Histopathological changes in the right lung were evaluated by hematoxylin-eosin (HE) staining. The relative expression of alpha-smooth muscle actin (α-SMA) and smooth muscle protein 22-alpha (SM22α) in each group was determined using real-time PCR.

RESULTSAt 35 days after surgery, the PH model and the solvent control groups had significantly higher mPAP and RV/LV+S than the blank control group, while the RAP 1 and the RAP 2 groups had significantly lower mPAP than the solvent control group (P<0.05). The RV/LV+S in the RAP 1 group was significantly lower than that in the solvent control group (P<0.05); however, there was no significant difference in RV/LV+S between the RAP 2 and the solvent control groups (P>0.05). HE staining in the right lung showed the substantially thickened pulmonary artery wall and narrowed arterial lumen in the PH model and the solvent control groups compared with the blank control group. Different degrees of reversal of the pulmonary artery wall thickening were observed after RAP administration. The results of real-time PCR revealed that the relative expression of α-SMA and SM22α in the PH model and the solvent control groups was significantly lower than in the blank control group, while the relative expression of α-SMA and SM22α in the RAP 1 and the RAP 2 groups was significantly higher than in the solvent control group (P<0.05).

CONCLUSIONSRAP can reverse the increase in pulmonary artery pressure and the right ventricular hypertrophy probably by regulation of the phenotypic conversion of vascular smooth muscle cells.

Actins ; genetics ; Animals ; Hemodynamics ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Hypertrophy, Right Ventricular ; etiology ; Male ; Microfilament Proteins ; genetics ; Muscle Proteins ; genetics ; Pulmonary Artery ; pathology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Sirolimus ; therapeutic use

Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH.
Animals ; Cytokines/metabolism ; Disease Models, Animal ; Endothelin-1/metabolism ; Fetal Blood/*cytology ; Gene Expression Regulation/drug effects ; Hemodynamics ; Humans ; Hypertension, Pulmonary/chemically induced/*therapy ; Hypertrophy, Right Ventricular/physiopathology ; Immunohistochemistry ; Lung/metabolism/pathology ; Male ; Matrix Metalloproteinase 2/metabolism ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*cytology/metabolism ; Monocrotaline/toxicity ; Nitric Oxide Synthase Type III/metabolism ; Pulmonary Artery/pathology ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin A/metabolism

OBJECTIVETo investigate the mechanism of how curcumin improves pulmonary vascular remodeling associated with chronic pulmonary arterial hypertension.

METHODSThe model of chromic hypoxia hypercapniapulmoary remodeling was made. Twenty-four male rats were randomly divided into 4 groups (n = 6): group I (normoxia control group), group II (hypxia and hypercapnia model group), group II (disodium cromoglycate control group), group IV (curcumin treated group). The last 3 group rats were put in a hypoxia cabin where the concentrate of O2 was 8% - 11% and the concentrate of CO2 was 3% - 5%, for 8 h a day and lasting 4 w in total. Group III rats were intraperitoneally injected with disodium cromoglycate (20 mg/kg) and group IV rats were administrated with curcumin by gavage (150 mg/kg). The morphological changes of pulmonary vessel walls and the ultrastructure of mast cells were observed by the optics microscope and the transmission electron microscope. Mast cells and its degranulation state were measured by toluidine blue staining and immunohistochemistry. Data were expressed as means ± SD (standard deviation) and analyzed with SPSS17.0 software.

RESULTS(1) By optics microscopy observation, the value of WA/TA was significantly higher in II group than other groups (P < 0.05). (2) Electron microscope showed that the endothelial cells of pulmonary arterioles in III and IV group were near to I group and the proliferation of pulmonary arterial media smooth cell layer and collagen fibers in adventitia was much lighter than those in II group. The membrane of mast cells was more intact in I, III, IV group than II group. (3) The number of mast cells, the degranulation rate of master cells and the number of positive tryptase stained cells in II group were significantly more than those in other groups. (P < 0.05).

CONCLUSIONCurcumin may inhibit the remodeling of pulmonary vessel induced by chronic hypoxia hypercapnia by mast cell regulation.

Animals ; Cell Degranulation ; Curcumin ; pharmacology ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; Hypoxia ; physiopathology ; Lung ; pathology ; Male ; Mast Cells ; physiology ; ultrastructure ; Pulmonary Artery ; drug effects ; Rats ; Rats, Sprague-Dawley ; Vascular Remodeling ; drug effects

BACKGROUNDCatestatin, a chromogranin A-derived peptide, is a potent antagonist of nicotine-evoked catecholamine release. We know that catecholamine plays an important role in cardiovascular remodeling induced by hypertension, therefore we hypothesized that catestatin would affect target-organ structure during hypertension.

METHODSTwelve spontaneously hypertensive rats (SHRs) were randomized to SHR control group and catestatin group, the normal control group was comprised of six healthy Wistar-Kyoto rats of the same age. Tail-cuff blood pressure and pulse rate were obtained at weeks 1, 4 and 8. At the end of the eight-week period, the heart, abdominal aorta and left kidney were excised and weighed, VG staining was done and the intima-media thickness of vessels and the collagen volume fraction were assessed by an image acquisition and analysis system. The proliferating cell nuclear antigen (PCNA) was observed by immunohistochemistry, and real time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of proliferative genes including cyclin A, ki67 and PCNA in the abdominal aorta.

RESULTSAll the parameters in SHR observed in the present study increased significantly compared to Wistar Kyoto rats (P < 0.01). With intervention with catestatin, the systolic blood pressure decreased slightly but it was not significantly different from the SHR control, the cardiac mass index and left ventricular mass index both decreased significant ly, the collagen volume fraction decreased by nearly 30% in the heart, by 25% in vessels and by 10% in the kidney, and the intima-media thickness and expression of proliferative genes, including cyclin A, ki67 and PCNA, in the abdominal aorta also decreased significant ly.

CONCLUSIONSThe present study indicated that catestatin could ameliorate proliferating changes of heart, kidney and vessels during hypertension, especially to the deposition of interstitial collagen. Blood pressure was not the main factor to mediate this effect, which suggested that catestatin could become a novel protective factor for hypertensive target organs.

Animals ; Aorta, Abdominal ; drug effects ; pathology ; Blood Pressure ; Cell Proliferation ; drug effects ; Chromogranin A ; pharmacology ; Heart Rate ; drug effects ; Hypertension ; drug therapy ; pathology ; physiopathology ; Kidney ; drug effects ; pathology ; Male ; Peptide Fragments ; pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

BACKGROUND/AIMS: Magnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats. METHODS: Fifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks. RESULTS: Systolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats. CONCLUSIONS: Concurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.
Aldosterone/blood ; Angiotensin II/blood ; Angiotensin II Type 1 Receptor Blockers/*pharmacology ; Animals ; Antihypertensive Agents/*pharmacology ; Biological Markers/blood ; Blood Pressure/*drug effects ; *Dietary Supplements ; Disease Models, Animal ; Hypertension/blood/*drug therapy/pathology/physiopathology ; Kidney/drug effects/pathology ; Magnesium/blood/*pharmacology ; Magnesium Deficiency/blood/*drug therapy/pathology/physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Systole ; Time Factors

BACKGROUNDEpidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.

METHODSSix-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.

RESULTSUrine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.

CONCLUSIONAngiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; pathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Losartan ; therapeutic use ; Male ; Orchiectomy ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole ; drug effects

BACKGROUNDDiabetic retinopathy (DR) has emerged as a leading cause of visual impairment and blindness in the working-aged population worldwide. This study aimed to assess frequency and associated factors of progression of DR in subjects with known diabetes in a population-based setting.

METHODSThe Beijing Eye Study is a population based study performed in Greater Beijing in 2001 and 2006. The present investigation included all subjects with known diabetes mellitus in 2001, who participated in the follow-up examination in 2006. Fundus photographs were assessed.

RESULTSThe study included 170 subjects; 51 (30%) subjects showed signs of DR in 2001 and were re-examined in 2006, 36 (21.2%) subjects (18 subjects with DR present at baseline, 18 subjects with newly diagnosed DR in 2006) showed a progression of DR during follow-up. Progression of DR was associated with rural region (odds ratio (OR): 5.43, P = 0.001) and self-reported arterial hypertension (OR: 3.85, P = 0.023). In the non-progressive subgroup, presence of DR was associated with different levels of education (< middle school, middle school, college or higher, OR: 0.30, P = 0.023), treatment modes of diabetes mellitus (OR: 10.24, P = 0.003) and cataract surgery (OR: 9.14, P = 0.007).

CONCLUSIONSIn a population-based setting in Greater Beijing, progression of DR occurred in 35% of subjects with pre-existing DR and overall in 21% of subjects with known diabetes within a 5-year period. Progression of DR was significantly associated with rural region and self-reported arterial hypertension. In the stable subjects, presence of DR was significantly associated with poor educational level, insulin treatment of diabetes and cataract surgery.

Adult ; Aged ; Aged, 80 and over ; China ; Diabetes Mellitus ; drug therapy ; physiopathology ; Diabetic Retinopathy ; epidemiology ; pathology ; Female ; Humans ; Hypertension ; physiopathology ; Insulin ; therapeutic use ; Male ; Middle Aged ; Multivariate Analysis

OBJECTIVETo observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH).

METHODSA multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment.

RESULTSAfter treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05).

CONCLUSIONSChinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.

Aged ; Aged, 80 and over ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Integrative Medicine ; Kidney ; drug effects ; pathology ; physiopathology ; Male ; Quality of Life ; Systole ; drug effects ; physiology

OBJECTIVETo observe the effect of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein (hs-CRP) in hypertensive patients with mild elevation of LDL-C.

METHODSSeventy-nine patients with a SBP of 140-179 mmHg and/or a DBP of 90-109 mmHg and mild elevated LDL-C were treated with rosuvastatin for 12 months (n=40) or not (n=39). The changes of hs-CRP, arteriosclerosis plaque and cardiac function at the end of the 12-months treatment relative to the baseline levels were analyzed.

RESULTSAfter 12 months of treatment, LDL-C was decreased by 33.2% in rosuvastatin group but remained unchanged in patients without rosuvastatin treatment. The left ventricular peak filling rate (LVPFR) increased significantly from 1.85 to 2.59 (P<0.05) and the serum levels of hs-CRP reduced significantly (P<0.05) after rosuvastatin treatment. The size of the plaques reduced significantly after a 12-month rosuvastatin therapy.

CONCLUSIONRosuvastatin therapy on the basis of conventional anti-hypertensive drugs can obviously improve the left ventricular diastolic function and produce favorable effects on arteriosclerotic plaques.

Aged ; Arteriosclerosis ; complications ; pathology ; C-Reactive Protein ; metabolism ; Cholesterol, LDL ; blood ; Female ; Fluorobenzenes ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hyperlipidemias ; drug therapy ; pathology ; physiopathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; therapeutic use ; Ventricular Function, Left ; drug effects