OBJECTIVE: To evaluate the efficacy and safety of blood-letting therapy (BLT) in treatment of hypertension. METHODS: A comprehensive electronic and manual bibliographic searches were performed in Cochrane Central Register of Controlled Trials, Excerpt Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Database to identify randomized controlled trials (RCTs) in which hypertensive patients were treated with BLT or BLT plus antihypertensive drugs (BPAD) against placebo, no treatment or antihypertensive drugs. The Cochrane Risk Assessment Tool was used to assess the methodological quality of trials. The Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 7 RCTs with 637 hypertensive patients from 1989 to 2017 were identified. Compared with antihypertensive drugs, blood pressure was significantly reduced by BLT (RR=1.21, 95% CI: 1.01 to 1.44, P=0.03; heterogeneity: P=0.06, I=60%) and BPAD (RR=1.25, 95% CI, 1.02 to 1.53, P=0.03; heterogeneity: P= 0.01, I=71%). Moreover, a significant improvement in Chinese medicine syndrome by BLT (RR=1.32; 95% CI: 1.14 to 1.53, P=0.0002; heterogeneity: P=0.53, I=0%) and BPAD (RR=1.47; 95% CI: 1.06 to 2.04, P=0.02; heterogeneity: P=0.13, I=56%) was identified. The reported adverse effects were well tolerated. CONCLUSION Although some positive findings were identified, no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design, significant heterogeneity, and insufficient clinical data. Further rigorously designed trials are warranted to confirm the results.
Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Bloodletting ; Combined Modality Therapy ; Humans ; Hypertension ; drug therapy ; physiopathology ; therapy ; Medicine, Chinese Traditional ; Middle Aged ; Randomized Controlled Trials as Topic ; Syndrome ; Treatment Outcome

BACKGROUNDAtherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance.

METHODSA total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed.

RESULTSFibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026.

CONCLUSIONSFbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; Aged ; Antihypertensive Agents ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Essential Hypertension ; blood ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Kidney Diseases ; blood ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; etiology ; physiopathology ; Risk Factors ; Serum Amyloid A Protein ; metabolism ; Stroke ; blood ; etiology ; physiopathology ; Tryptases ; blood

PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
Acute Disease ; Aged ; Antihypertensive Agents/*administration & dosage ; Blood Pressure/drug effects ; Cause of Death ; Female ; Heart Failure/*drug therapy/physiopathology ; Heart Rate/drug effects/physiology ; Hemodynamics ; Humans ; Hypertension/*drug therapy/physiopathology ; Injections, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Nitroglycerin/administration & dosage ; Peptide Fragments/blood ; Piperazines/*administration & dosage ; Ventricular Function, Left/drug effects/physiology

Angiotensin II (Ang II) is involved in endothelium injury during the development of hypertension. Tribulus terrestris (TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats (SHRs) and its protective effects against Ang II-induced injury in human umbilical vein endothelial cells (HUVECs). SHRs were administered intragastrically with TT (17.2 or 8.6 g·kg·d) for 6 weeks, using valsartan (13.5 mg·kg·d) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang II, endothelin-1 (ET-1), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10 mol·L Ang II. Cell Apoptosisapoptosis, intracellular reactive oxygen species (ROS) was assessed. Endothelial nitric oxide synthase (eNOS), ET-1, SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang II, ET-1, NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang II-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mRNA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.
Angiotensin II ; metabolism ; Animals ; Antihypertensive Agents ; administration & dosage ; Apoptosis ; drug effects ; Blood Pressure ; drug effects ; Endothelium, Vascular ; drug effects ; metabolism ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; NF-kappa B ; genetics ; metabolism ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Plant Extracts ; administration & dosage ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reactive Oxygen Species ; metabolism ; Tribulus ; chemistry

Alkaloids from Ba lotus seeds (ABLS) are a kind of important functional compounds in lotus seeds. The present study was designed to determine its hypertension prophylactic effects in the L-NNA-induced mouse hypertension model. The mice were treated with ABLS, the serum and tissues levels of NO, MDA, ET-1, VEGF, and CGRP were determined using the experimental kits, the mRNA levels of various genes in the heart muscle and blood vessel tissues were further determined by RT-PCR assay. ABLS could reduce the systolic blood pressure (SBP), mean blood pressure (MBP), and diastolic blood pressure (DBP), compared to that of the model control group. After ABLS treatment, the NO (nitric oxide) contents in serum, heart, liver, kidney and stomach of the mice were higher than that of the control mice, but the MDA (malonaldehyde) contents were lower than that of the control mice. The serum levels of ET-1 (endothelin-1), VEGF (vascular endothelial growth factor) were decreased after ABLS treatment, but CGRP (calcium gene related peptide) level was increased. The ABLS treated mice had higher mRNA expressions of HO-1, nNOS, and eNOS and lower expressions of ADM, RAMP2, IL-1β, TNF-α, and iNOS than the control mice. Higher concentration of ABLS had greater prophylactic effects, which were close to that of the hypertension drug captopril. These results indicated the hypertension prophylactic effects of ABLS could be further explored as novel medicine or functional food in the future.
Alkaloids ; administration & dosage ; Animals ; Blood Pressure ; drug effects ; Disease Models, Animal ; Humans ; Hypertension ; chemically induced ; drug therapy ; metabolism ; physiopathology ; Interleukin-1beta ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitroarginine ; Nymphaeaceae ; chemistry ; Seeds ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

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

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

BACKGROUNDDespite a recent American Heart Association (AHA) consensus statement emphasizing the importance of resistant hypertension (RH), its control is still a challenge for conventional medicine. The Chinese herbal formula, Qutan Huayu Fang, has been used effectively to assist antihypertensive agents in blood pressure control, but its effect for RH patients is still unclear. This pilot study aims to explore the effects of taking the formula in addition to antihypertensive medication in the management of RH.

METHODS/DESIGNA prospective cohort study will be conducted in two first-class hospitals of traditional Chinese medicine (TCM). Eligible RH patients will be classified as the experimental group (n = 100) and the control group (n = 100) based on the interventions they receive. Participants taking antihypertensive agents and the Chinese herbal formula will be in the experimental group and those taking antihypertensive agents alone will be in the control group. The whole study will last 24 weeks, including an 8-week observation and follow-up at 24 weeks. The primary outcomes, assessed against patient baseline conditions, will be the reduction of systolic blood pressure and diastolic blood pressure as well as changes in TCM symptoms and signs. These outcomes will be assessed at weeks 2, 4, 6, and 8. The reductions of blood pressure will also be assessed at week 24. Cardiac events and mortality rate will be secondary outcomes and will be assessed at weeks 8 and 24. Any adverse reactions will be recorded during the study. The causal inference method will be used to assess the effectiveness of the inclusion of TCM herbal medicine in the management of patients with RH.

DISCUSSIONThis study will determine whether the Chinese herbal formula is helpful for RH patients treated with antihypertensive agents and the findings will provide a basis for further confirmatory studies.

Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Clinical Protocols ; Cohort Studies ; Drug Resistance ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Pilot Projects ; Plants, Medicinal ; Prospective Studies ; Treatment Outcome

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

Multi-component traditional Chinese medicines are an innovative research mode for traditional Chinese medicines. Currently, there are many design methods for developing multi-component traditional Chinese medicines, but their common feature is the lack of effective connection of the traditional Chinese medicine theory. In this paper, the authors discussed the multi-component traditional Chinese medicine design methods based on medicinal property combination modes, provided the combination methods with the characteristics of traditional Chinese medicine for the prescription combinations, and proved its feasibly with hypertension cases.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Blood Pressure ; drug effects ; Drug Combinations ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Hypertension ; drug therapy ; physiopathology ; Medicine, Chinese Traditional ; Rats