Animals ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hypertension ; drug therapy ; pathology ; physiopathology ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Phytotherapy ; Ventricular Remodeling ; drug effects

OBJECTIVETo evaluate the effect of Ginkgo biloba extract (EGb) on hepatic microcirculation and portal hypertension in CCl4 treated rats.

METHODSTwenty-five male Wistar rats were divided into a blank, a CCl4 treated and a CCl4 plus EGb treated group, and all were treated for 10 weeks. The free portal vein pressures were measured through catheterizations. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were studied with transmission electron microscopy. The amounts of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF), nitric oxide (NO), cNOS and iNOS in the liver tissues were determined.

RESULTSThe portal vein pressure of the CCl4 plus EGb treated group was (7.4 +/- 0.6) mm Hg while the pressure of the CCl4 treated group was (8.7 +/- 0.8) mm Hg. Aggregation of blood cells or microthrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and spaces of Disse, injury of endothelial cells and capillarization of hepatic sinusoid were significantly milder in the EGb group. The amounts of MDA, ET-1, PAF, NO and iNOS were markedly lower in the CCl4 plus EGb treated group than in the CCl4 treated group.

CONCLUSIONThe results demonstrated that EGb can decrease the portal vein pressure and improve hepatic microcirculation in CCl4 treated rats. The mechanisms of this effect may involve its inhibition on ET-1, PAF, lipid peroxidation, and down regulation of the hepatic iNOS and NO expressions.

Animals ; Ginkgo biloba ; Hepatic Veins ; pathology ; Hypertension, Portal ; drug therapy ; physiopathology ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; pathology ; physiopathology ; Male ; Microcirculation ; drug effects ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar

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

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

OBJECTIVEPulmonary hypertension is a proliferative vascular disease characterized by pulmonary vascular structural remodeling. Until now, the pathogenesis of pulmonary hypertension is still not fully understood. Although considerable progress has been made, there is, to date, no cure for advanced pulmonary vascular disease. Recently, a number of studies suggest that endogenous vascular elastase (EVE) play a role in the vascular changes associated with pulmonary hypertension. The purpose of the study was to determine whether an elastase inhibitor might reverse advanced pulmonary vascular disease produced in rats by injection of monocrotaline.

METHODSOne hundred and twenty male Sprague-Dawley rats were used in this study. The rats were divided into three groups: control, model and ZD-0892 groups. In the model and ZD-0892 groups, the rats were subjected to a single subcutaneous injection of monocrotaline (60 mg/kg) in the hind flank, while the rats in control group received an equivalent volume of 0.9% saline. From day 21, the rats in the ZD-0892 and model groups received twice-daily gavage tube feedings of either ZD-0892 at a dose of 240 mg/kg per day or its administration vehicle, while the rats in control group were subjected to an equivalent volume of 0.9% saline. On days 21, 28 and 35 post-injection, the elastolytic activity was measured with a fluorescence microplate reader and pulmonary artery pressure was detected via catheterization. Meanwhile, the lungs were evaluated morphologically, using the barium-gelatin perfusion technique.

RESULTSThe injection of monocrotaline led to severe pulmonary hypertension in rats 21 days later and pulmonary artery elastolytic activity increased remarkably. A 1-week treatment with ZD-0892 resulted in declines in elastase activity. This was associated with significant declines in pulmonary artery pressure, decreases in muscularization of peripheral arteries and reductions in medial hypertrophy. After 2 weeks, elastase activity returned to normal level. Pulmonary artery pressure and structure were normalized.

CONCLUSIONIncreased elastase activity is important in the development of vascular changes and progressive pulmonary hypertension. ZD-0892 can suppress the elastase activity and completely reverse the fatal pulmonary hypertension induced by monocrotaline in rats.

Animals ; Hypertension, Pulmonary ; chemically induced ; drug therapy ; Male ; Monocrotaline ; toxicity ; Pancreatic Elastase ; antagonists & inhibitors ; Pulmonary Artery ; drug effects ; pathology ; physiopathology ; Pyrroles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; pharmacology

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 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

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

OBJECTIVETo observe the effect of Wendan Xiezhuo method (WXM) on carotid arteriosclerosis and vascular endothelial diastolic function in essential hypertension (EH) patients with turbid-phlegm syndrome (TPS).

METHODSForty-three EH patients of medium and low risk with TPS were randomly assigned to two groups, the Wendan Tablet (WT) group (23 cases) and the placebo group (20 cases), they were treated with WT and placebo respectively on the base of amlodipine treatment to control the blood pressure. Carotid intimamedia thickness (IMT), atherosclerotic plaque score of carotid artery, endothelium-dependent dilation (EDD) and flow-mediated vasodilation (FMD) of brachial artery after taking nitroglycerin were detected with ultrasonography before and after 6 months of treatment.

RESULTSAs compared with those in the placebo group, in the WT group after treatment, scores of TPS and carotid plaque were better, area of carotid plaque was lesser and IMT was lower significantly (P<0.05 or P<0.01). There was a negative correlation between brachial artery EDD and carotid IMT in EH patients with TPS (r = - 0.596, P < 0.05). After treatment EDD was improved more significantly in the WT group than that in the placebo group, however, no significant difference was found in non-endothelium-dependent dilation between the two groups.

CONCLUSIONA negative correlation exists between brachial artery EDD and carotid IMT, and the latter could be aggravated by TPS in EH patients. WXM shows favorable effects in improving carotid plaque and EDD.

Aged ; Atherosclerosis ; complications ; pathology ; physiopathology ; Carotid Arteries ; diagnostic imaging ; drug effects ; physiopathology ; Carotid Artery Diseases ; complications ; diagnostic imaging ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Female ; Humans ; Hypertension ; complications ; drug therapy ; pathology ; Male ; Middle Aged ; Phytotherapy ; Syndrome ; Treatment Outcome ; Ultrasonography

BACKGROUND: Increased aortic stiffness measured by pulse wave velocity (PWV) and left ventricular hypertrophy (LVH) are independent risk factors of cardiovascular events in hypertensive patients. We have conducted a prospective study to examine the effects of the angiotensin II receptor antagonist (irbesartan) on PWV and LVH in hypertensive patients. METHODS: A total of 52 untreated hypertensive patients (age:53.3+/-8.0 yrs) were enrolled; they had no evidence of associated cardiovascular complications. Blood pressure, heart rate, aortic PWV and left ventricular mass index (LVMI) by 2-D echocardiography were measured at baseline and after irbesartan treatment (150 mg or 300 mg/day) at 12 weeks and 24 weeks. RESULTS: Blood pressure was significantly decreased after 12 weeks and 24 weeks of treatment compared to baseline (SBP: 134.6+/-13.3 mmHg, 134.0+/-11.0 mmHg vs 163.7+/-13.8 mmHg p<0.001, DBP: 86.0+/-10 mmHg, 83.07 mmHg vs 102.4+/-9.6 mmHg p<0.001, respectively) without significant change in heart rate. LVMI decreased at 12 weeks and at 24 weeks after treatment compared to baseline (from 145.5+/-35.1 g/m2 at baseline to 137.5+/-35.4 g/m2 at 12 weeks, p=0.017 and 135.3+/-35.4 g/m2 at 24 weeks, p=0.008). Aortic PWV was decreased after irbesartan treatment at 12 weeks (from 9.6+/-2.8 m/sec to 8.7+/-3.1 m/sec at 12 weeks, p=0.064) and at 24 weeks (from 9.6+/-2.9 m/sec to 7.7+/-2.1 m/sec at 24 weeks, p=0.007). CONCLUSIONS: Long-term treatment with irbesartan may reduce arterial stiffness and regression of LVH in hypertensive patients. The pleiotropic effects of irbesartan, further decreasing PWV without change of BP between 12 and 24 weeks of treatment, may have favorable vascular effects on arterial stiffness and LVH.
Tetrazoles/*therapeutic use ; Prospective Studies ; Middle Aged ; Male ; Hypertrophy, Left Ventricular/*prevention & control ; Hypertension/*drug therapy/pathology/physiopathology ; Humans ; Female ; Biphenyl Compounds/*therapeutic use ; Aorta/*drug effects/physiopathology ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Aged ; Adult