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Objective: To provide experimental evidence for the antihypertensive activity of the flavonoids in flower buds of Coreopsis tinctoria (CT-F) and to investigate the underlying mechanism. Methods: The spontaneously hypertensive rats (SHRs) were divided into model, captopril (positive control), and CT-F groups, and the Wistar-Kyoto rats were set as control group, eight in each group. The blood pressure of SHRs, the activity of angiotensin II (Ang-II) in plasma, nitric oxide (NO), malondialdehyde (MDA) and thoracic aorta media thickness in SHRs were measured by tail-cuff method, radioimmunity method, nitrate reductase method, thibabituric acid (TBA) method, and the hematoxylin-eosin staining method. Q-PCR analysis was performed to determine the relative quantity of angiotensin-converting enzyme (ACE), ACEII, angiotensin type 1 receptor (AT1R), and TGF-β1 mRNA in left ventricle. Results: CT-F could lower the systolic blood pressure of SHRs dramatically (P < 0.01). The levels of MDA in serum and Ang II in plasma of SHRs treated with CT-F decreased markedly (P < 0.05, 0.01), the level of NO in serum increased significantly (P < 0.01). In addition, thoracic aorta media thickness in SHRs treated with CT-F was thinner than that of the model group (P < 0.05). The mRNA expression of ACE, AT1R, and TGF-β1 in left ventricle was markedly decreased (P < 0.05), while that of ACE II was increased (P < 0.05). Conclusion: CT-F is effective to lower the blood pressure of SHRs, and its antihypertensive effect is probably associated with lowering the oxidative stress by reducing MDA, ameliorating aorta remodeling, dilating vessel by increasing NO and decreasing Ang-II, and regulating the expression of rennin-angiotensin System-related various genes. © 2014 Tianjin Press of Chinese Herbal Medicines.
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The majority of hypertensive patients do not achieve target blood pressure for a variety of reasons, including insufficient medication, drug resistance, and noncompliance. There remains a significant need to develop new agents to better control hypertension. Nebivolol is a third-generation beta-adrenergic receptor blocker which is very highly cardioselective and has direct vasodilator properties via stimulation of endothelial nitric oxide synthase activity. Aliskiren is the first orally active inhibitor of renin as an antihypertensive agent. It is associated with dose-related falls in blood pressure comparable to other major classes of antihypertensive drugs with a placebo level of side effects. Endothelin is a powerful vasoconstrictor peptide. An endothelin-receptor antagonist such as bosentan significantly lowered blood pressure in patients with essential hypertension. Vasopeptidase inhibitors inhibit neutral endopeptidase and angiotensin converting enzymes, but side-effects such as angio-oedema and cough remain to be overcome. AngQb vaccine in hypertensive patients showed a marked reduction in early morning blood pressure without serious adverse events.
Subject(s)
Humans , Amides , Angiotensins , Antihypertensive Agents , Benzopyrans , Blood Pressure , Cough , Drug Resistance , Endothelins , Ethanolamines , Fumarates , Hypertension , Nebivolol , Neprilysin , Nitric Oxide Synthase Type III , Renin , SulfonamidesABSTRACT
Objective To investigate the changes in circulatory and pulmonary monary angiotensinⅡin rats with acite lung injury(ALI)and explore the role of angiotensinⅡin ALI.Method Thirty S-D rats were randomly divided into control group(n=6)and ALI group(n=24).The ALI group was further divided into four subgroups of observation at various intervals,3,6,9 and 12 hours after administration of lipopolysaccharide (LPS)into the femoral vein(each n=6).The indices rate,blood gas analysis,wet weight/dry weight(W/D)ratio of lung lobes,and pathological changes were successively observed at 3,6,9,and 12 hours after injury.The content of angiotensinⅡin lung tissue and blood plasma were detected at above set intervals by radioimmunoassay.Data of these assays were analyzed by one-factor analysis of variance.Results Compare with the control group,pH and PaO2 of arterial blood in ALI group decreased significantly(P＜0.05)at all intervals and PaCO2 of arterial blood in ALI group decreased significanfly(P＜0.05).at all intervals and PaCO2 of arterial blood and lung W/D weight ratio increased significantly(P＜0.05),and scores of lung histopathology denoted the lung injuried(P＜0.01).After injury of lung,angiotensin Ⅱ content increased markedly in lung homogenate and blood plasma (P＜0.05).Angiotensin Ⅱ content in blood plasma reached peak value at 9 hours,and content of angiotensin Ⅱ in lung homogenates kept on increasing at allintervals of observation.Conclusions A large amount of angiotensin Ⅱ releases into lung tissue and blood plasma during ALI,suggesting systemic and pulmonary rennin-angiotensin systems are activated.
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0.05).There were significant difference between pre-operation and after-operation in GA group(P
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Objective:To explore the molecular mechanism of Gold Theragran in the protection of renal function,and the inhibition of renal local rennin angiotensin(RA)system in the early diabetic nephropathy(DN),and to provide the theoretical and experimental data for clinical application to prevent the DN.Methods:The experimental rats consisted of 64 healthy SD rats,average 180-220g,female and male both a half,rat model of DN was established by improved method of YANG Junwei,s method of intraperitoneal injection of STZ after nephrectomy.8 Rats was taken as normal group,the rest of them were randomly divided into 5 groups:high,middle and low dose groups of Gold Theragran,Valsartan group,model group.In each group,blood glucose,blood lipids,urine microalbumin per 24 hours,KW/BW,renal angiotensin converting enzyme,plasma and renal angiotensin Ⅱ,and its type 1 receptor were observsd and measured.Results:①Rat's general status in each treatment group was improved compared with the DN model group.②The levels of serum glucose decreased in all treatment groups,especially the high-dose group and mid-dose group were significant(P0.05).③The levels of abnormally high lever of TG,TC decreased in treatment groups,especially the high-dose group and mid-dose group were significant(P0.05).The high-dose group had further function to regulate the lipids in the 28th day than in the 7th day(P0.05).Conclusion:Firstly,Gold Theragran had a therapeutic effect of protecting the renal function on the experimental DN rats;Secondly,Gold Theragran can inhibit the abnormal state of activated rennin angiotensin system in diabetic nephropathy,delay the development of diabetic nephropathy;Thirdly,with the treatment course prolonged,the effective of Gold Theragran might be more obvious,and different dose groups show dose-effect-dependent relationship.
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Cardiovascular disease is the most important factor that affect the lifetime of uremia patients. Recently, scientists pay closer attention to study the mechanism of cardiac injury in uremia patients. In this article, we will make an overview on mechanism of cardiac injure caused by uremia toxin, secondary hyperparathyroidism, calcium-phosphorus metabolic disorder, rennin-angiotensin-aldosterone system.