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Background: Although left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the predialysis period has not been fully examined. Methods: We measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study in order to identify factors that are associated with increased LVMI in patients with stage 3-5 CKD. LVH was defined as LVMI > 125 g/m in male patients and >110 g/m in female patients. Results: We analyzed baseline characteristics in 1185 participants (male 63.7 %, female 36.3 %). Diabetes mellitus was the underlying disease in 41.3 % of patients, and mean age was 61.8 ± 11.1 years. LVH was detected in 21.7 % of patients at baseline. By multivariate logistic analysis, independent risk factors for LVH were past history of cardiovascular disease (odds ratio [OR] 0.574; 95 % confidence interval [CI] 0.360-0.916; P = 0.020), systolic blood pressure (OR 1.179; 95 % CI 1.021-1.360; P = 0.025), body mass index (OR 1.135; 95 % CI 1.074-1.200; P < 0.001), and serum calcium level (OR 0.589; 95 % CI 0.396-0.876; P = 0.009). Conclusion: Cross-sectional baseline data from the CKD-JAC study shed light on the association between LVH and risk factors in patients with decreased renal function. Further longitudinal analyses of the CKD-JAC cohort are needed to evaluate the prognostic value of LVH in CKD patients. [ABSTRACT FROM AUTHOR]

Abstract: As a development strategy for backups of Fimasartan (1), a comparative molecular similarity indices analysis (CoMSIA) of a set of sixty-five 5-(biphenyl-2-yl)-1H-tetrazole derivatives has been performed to find out the pharmacophore elements for angiotensin II receptor type 1 (AT1) blockade. The most potent compound containing pyrimidin-4(3H)-one ring, Fimasartan (1) was used to align the molecules. As a result, we obtained 3D-QSAR model which provided good predictivity for both the training set (q 2 =0.846, r 2 =0.975) and the external test set . This model would guide the design of backups for Fimasartan (1), a launched oral antihypertensive agent. [Copyright &y& Elsevier]

BACKGROUND We conducted a study to determine the joint association of physical activity, pharmacologic treatment for hypertension, and the control of blood pressure (BP) on all-cause mortality risk. METHODS The study subjects were 10,665 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and the Continuous NHANES survey (1999–2000 and 2000–2001). Cox proportional hazards analyses were used to estimate differences in mortality risk according to physical activity, pharmacologic treatment for hypertension, and BP control, with physically active, treated, and controlled as the referent category. RESULTS The average follow-up time in the study was 8.6±4.8 years. The main effect of physical activity was significant independently of pharmacologic treatment and BP control (P < 0.001). Physically inactive adults with hypertension had a higher risk of mortality than did physically active adults with treated and controlled hypertension (inactive, treated and controlled hypertension: HR, 1.42; 95% CI, 1.17–1.72; P < 0.01; inactive, treated, and uncontrolled hypertension: HR, 1.55; 95% CI, 1.30–1.84; P < 0.01; inactive, untreated, and uncontrolled hypertension: HR, 1.27; 95% CI, 1.07–1.52, P < 0.01). However, the risk of mortality for physically active adults with hypertension did not differ significantly with or without treatment for hypertension if their hypertension remained uncontrolled (active, treated and uncontrolled hypertension: HR, 1.17; 95% CI 0.98–1.40; P = 0.08; active, untreated and uncontrolled hypertension: HR, 0.90; 95% CI, 0.76–1.08; P = 0.25). Physically active, normotensive individuals had a lower all-cause mortality risk than did the referent group of physically active individuals being treated with antihypertensive medication and who had controlled hypertension (HR, 0.72; 95% CI, 0.60–0.86; P < 0.01), whereas physically inactive, normotensive individuals had a risk of mortality similar to that of the referent group (HR, 1.08; 95% CI, 0.90–1.30; P = 0.42). CONCLUSION Physical activity may be as or even more important than pharmacotherapy for reducing the risk of mortality in adults with hypertension. However, the risk of mortality remained higher for physically active adults with treated and controlled hypertension than did the risk of mortality for physically active normotensive populations. Prevention of hypertension is therefore imperative for reducing the all-cause risk of premature mortality in adults. [ABSTRACT FROM AUTHOR]

Losartan is an antihypertensive agent that lost its patent protection in 2010, and, consequently, it has been available in generic form. The latter motivated the search for a rapid and precise alternative method. Here, a simple conductometric titration in aqueous medium is described for the losartan analysis in pharmaceutical formulations. The first step of the titration occurs with the protonation of losartan producing a white precipitate and resulting in a slow increase in conductivity. When the protonation stage is complete, a sharp increase in conductivity occurs which was determined to be due to the presence of excess of acid. The titrimetric method was applied to the determination of losartan in pharmaceutical products and the results are comparable with values obtained using a chromatographic method recommended by the United States Pharmacopoeia. The relative standard deviation for successive measurements of a 125 mg L (2.71×10 mol L) losartan solution was approximately 2%. Recovery study in tablet samples ranged between 99 and 102.4%. The procedure is fast, simple, and represents an attractive alternative for losartan quantification in routine analysis. In addition, it avoids organic solvents, minimizes the risk of exposure to the operator, and the waste treatment is easier compared to classical chromatographic methods. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Coumarin molecule is used as anticoagulant. Other uses like anti-HIV, anti-tumor, anti-hypertensive, anti-arrhythmia, anti-osteoporosis, pain relief increase research of coumarin derivative. Perkin discovered a synthetic method of coumarin and opened the door in synthetic research. Now a days there are so many methods are use to form coumarin. Warfarin is a well known drug of 4-hydroxy coumarin derivative. It is consider that, propranolol drug act as a lead molecule of β-blocker. Alkylaminohydroxypropoxy side chain is responsible for β-blocking activity in propranolol. Hence synthesis and it's characterization of antihypertensive coumarin derivative was our main target. [ABSTRACT FROM AUTHOR]

Abstract: We synthesized and evaluated inhibitory activity against T-type Ca2+ channels for a series of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives. Structure–activity relationship studies have revealed that dialkyl substituents at the benzylic position play an important role in increasing inhibitory activity. Oral administration of N-[2-ethyl-2-(4-fluorophenyl)butyl]-1-(2-phenylethyl)piperidine-4-carboxamide (20d) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, which is often caused by traditional L-type Ca2+ channel blockers. [Copyright &y& Elsevier]

Aims: Transdermal therapeutic systems were developed using the polymers, Eudragit E 100 and polyvinyl pyrrolidone VA 64 in a film casting assembly. The medicated films were evaluated for physical properties, in vitro drug release studies, in vitro skin permeation studies, and pharmacodynamic studies. Results: The physical parameters were found to be very satisfactory with high drug content (>99%). The in vitro drug release studies were performed using paddle-over-disc assembly specified in USP XXIII. The pharmacodynamic studies were carried out using tail cuff method in Wistar albino rats. Hypertension was induced by methyl prednisolone acetate subcutaneously for 2 weeks. The developed matrix patch was found to decrease the blood pressure (25.42% reduction in mean systolic blood pressure of rats) significantly (P < 0.001) in proximity of the normal value and it was maintained for 24 hours. Conclusion: It can be concluded that the developed transdermal matrix patch holds promise for the management of hypertension that needs to be validated by clinical trials. [ABSTRACT FROM AUTHOR]

BackgroundClinical trials have provided convincing evidence that blood pressure (BP) lowering treatment reduces the risk of cardiovascular disease (CVD) and total mortality. The objective of this study was to examine the association of hypertension treatment, control, and BP indexes with all-cause and cardiovascular mortality among US adults with hypertension.MethodsPersons aged ≥18 years from the Third National Health and Nutrition Examination Survey (NHANES III) were identified as hypertensives based on a BP ≥140/90 mm Hg or current treatment for hypertension. Vital status in 2006 was ascertained by passive follow-up using the National Death Index. Cox regression models were used to assess correlates of survival.ResultsAt baseline, 52% of hypertensive adults reported currently taking prescription medicine for high BP and 38% of treated persons had BP controlled. Compared to treated controlled hypertensives, treated uncontrolled hypertensives had a 1.57-fold (95% confidence interval (CI) 1.28–1.91) and 1.74-fold (95% CI 1.36–2.22) risk of all-cause and cardiovascular mortality; untreated hypertensives had a 1.34-fold (95% CI 1.12–1.62) and 1.37-fold (95% CI 1.04–1.81) risk of all-cause and cardiovascular mortality, respectively. The association persisted after further excluding persons with pre-existing hypertension comorbidities. Mortality risk was linearly increased with systolic BP (SBP), pulse pressure (PP), and mean arterial pressure (MBP), whereas diastolic BP (DBP) was not a significant predictor of cardiovascular mortality overall. No significant associations were observed between drug classes and mortality risk.ConclusionsThis study indicates that uncontrolled and untreated hypertension was associated with increased risk of total and cardiovascular mortality among the general hypertensive population.American Journal of Hypertension 2010; doi:10.1038/ajh.2009.191 [ABSTRACT FROM AUTHOR]

The authors discuss whether patients with cardiovascular risk factors, from an antagonist view from the Heart Outcomes Evaluation-3 (HOPE-3) Trial, should receive intensive treatment of hypertension to <120/80 mm Hg target. They say that epidemiologic studies demonstrate a graded rise in risk at systolic blood pressure (BP) >115 mmHg and diastolic BP >75 mmHg.

OBJECTIVE:To investigate the pharmaceutical care for patients with diabetic nephropathy by clinical pharmacists. METHODS: The clinical pharmacists participated into the formulation of antihypertensive therapeutic scheme to one patient with diabetic nephropathy, and monitored the whole process of treatment for the patient. RESULTS: After the partner treatment of clinical pharmacists and clinicians, the blood pressure level of the patient were in normal range. Through the pharmaceutical care by clinical pharmacists, medication compliance of the patient were improved, and incidence of adverse drug reactions were induced. CONCLUSIONS: The clinical pharmacists participate into the clinic and keep an eye on the medication of patients and propose optimized therapeutic scheme, all of which play important roles in elevating curative effects and promoting the rational drug use. [ABSTRACT FROM AUTHOR]

Diabetes causes approximately 2.9 million deaths yearly, mainly through an increased risk of cardiovascular disease. In hypertensive diabetics, blood pressure reduction determines a significantly lower rate of cardiovascular and renal events. Conversely, reaching the generally recommended target of lower than 130/80 mmHg is a difficult challenge and, in most cases, two or more antihypertensive drugs are required. Until recently, there was a general consensus that combination treatment should include a diuretic as one of the two fundamental agents. However, recently published trials using calcium channel blockers plus renin-angiotensin systemblocking agents showed that such a combination reduces the risk of major cardiovascular events, provides greater renoprotection, and improves metabolic outcomes as compared with diureticbased combinations. The present review explores the potential for an 'optimal' combination therapy in patients with diabetes mellitus and hypertension, in view of recent experimental and clinical evidence. [ABSTRACT FROM AUTHOR]

R5684 --> 701.8 --> Hypertension is a chronic cardiovascular disease of extreme and important global concern. It has been established as a leading cause of death especially in humans. The aim of this study was to evaluate the possible antihypertensive effect of a common locally available plant Morinda lucidaagainst L‐Nitro‐Arginine‐Methyl‐Ester (L‐NAME)‐induced hypertension in male Wistar rats. Forty‐eight rats were used for the experiment. They were divided into six groups labelled A‐F, each containing eight animals. The animals were dosed for six weeks with group A being the control group (normotensive) given feed and water ad libitun; Group B animals were administered L‐NAME only, 40 mg/kg (hypertensive); Groups C, D and E were simultaneously treated with L‐NAME (40 mg/kg) and Morinda lucida extract in increasing doses of 100 mg/kg, 200 mg/kg and 400 mg/kg, respectively, while Group F were given lisinopril at 20 mg/kg for a period of 6 weeks. From the result, there was significant increase in systolic, diastolic, and mean arterial blood pressure in the hypertensive group compared to the normotensive group and hypertensive treated groups. Hypertension caused significant (p<0.05) increases in oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (PC), hydrogen peroxide (H2O2), while reducing the activities of superoxide dismutase (SOD), and serum nitric oxide (NO) levels. Also, serum myeloperoxidase (MPO), blood urea nitrogen and creatinine were increased with high expression of cardiac injury biomarkers such as cardiac troponin and angiotensin 2 type 1 receptor. These indicated oxidative stress, cardiac damage because of hypertension, most especially in the untreated hypertensive group. The co‐treatment of hypertensive rats with Morinda lucida extract caused reduction in markers of oxidative stress and inflammation and normalized blood pressure parameters. The findings from this study suggest the possibility of using Morinda lucida extract as a novel antihypertensive agent. [ABSTRACT FROM AUTHOR]

Overall, approximately 40% of diabetic patients have hypertension at the time of diagnosis of diabetes and a similar percentage may develop hypertension during their follow-up. Factors contributing to this high prevalance of hypertension in diabetes include obesity, old age, insulin resistance, increased extracelluar volume, diabetic nephropathy and increased arterial stiffness. Well-conducted clinical trials that have been completed in the last decade demonstrated a major impact of hypertension on the micro- and macrovascular complications of diabetes and remarkable benefits of its control. Based on this large trial database, the currently accepted level of blood pressure used in diabetes for definition and target of therapy is 130/80 mmHg. Dietary and behavioral lifestyle modifications should be an intergral part of any management regimen. These include weight reduction, low sodium diet, exercise, moderate alcohol intake and smoking cessation. Effective control of blood pressure to target levels is more important than the drug(s) used. Combination drug therapy is needed frequently to achieve a target blood pressure. Although blockers of the renin-angiotensin-aldosterone system seem to have a favorable effect in diabetes, high-level evidence suggests that low-dose thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers are all good choices, both as initial and add-on therapy. Frequently, more than one drug is needed, and a low-dose thiazide diuretic combined with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker is a commonly used effective combination. Other drugs that can be added include calcium channel blockers and β-blockers. In certain clinical situations, specific drug classes are indicated. These include angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in the case of diabetic nephropathy, β-blockers in the case of ischemic heart disease, and calcium channel blockers and loop diuretics in the case of advanced renal insufficiency, where the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers carries a significant risk of hyperkalemia. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Research in Cardiology Supplements is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) published its main findings in December, 2002. It recommended thiazide diuretics as a first-line treatment of hypertension. The current study describes the prescribing patterns of thiazide diuretics in four regions of Kaiser Permanente, a large national United States Health Maintenance Organizatoin—two regions that had an ALLHAT clinical center and two that did not. We tested the hypothesis that participation in a clinical trial leads to quicker and greater adoption of study recommendations than non-participation in a trial. The relative percentage of filled outpatient prescriptions for the period 2 or 3 years before the ALLHAT main publication through December 31, 2004 was calculated by region for thiazide-type diuretics and for calcium channel blockers (CCBs), β-blockers, central α-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and other antihypertensive diuretics. In the 2 years after publication of the ALLHAT trial findings, the percentage of all prescriptions for thiazide diuretics increased from 11.2% to 12.4% in the two regions with an ALLHAT clinical site and from 8.9% to 10.1% in the two regions without an ALLHAT clinical site (p >0.05). The percentage of new prescriptions for thiazide diuretics increased from 13.7% to 16.6% in the two regions with an ALLHAT clinical site and from 10.8% to 13.0% in the two regions without an ALLHAT clinical site (p >0.05). Participation in a clinical hypertension study does not appear to accelerate adoption of study recommendations. [Copyright &y& Elsevier]

In an effort to assess the cardiovascular benefits of combined angiotensin receptor blockage and calcium channel antagonism, we assessed the chronic effects of the angiotensin type 1 receptor blocker candesartan, the calcium channel blocker benidipine, and the use of a combination therapy in Dahl salt-sensitive (DS) rats. DS rats receiving a high salt diet were treated with either benidipine (4 mg/kg), candesartan (1 mg/kg) or both. Rat blood pressure was measured using a tail-cuff method. Following 12 weeks, the effect on heart weight, plasma-oxidized low-density lipoprotein (ox-LDL) level, endothelium-dependent vasorelaxation, and histology of the heart and aorta was assessed. Blood pressure, heart weight and plasma ox-LDL levels increased, while endothelium-dependent vasorelaxation decreased in the DS rats. Candesartan and benidipine inhibited the increase in blood pressure and heart weight, and the decrease in endothelium-dependent vasorelaxation. The use of benidipine alone or a combination significantly inhibited the increase in ox-LDL levels, whereas candesartan alone had no significant effect on ox-LDL levels. The present findings indicate that, if the monotherapy using ARB could not achieve adequate control of blood pressure, the combination therapy with ARB and benidipine provides the additional reductions in hypertension and cardiac hypertrophy. Moreover, the combination therapy inhibits cardiovascular dysfunction and ox-LDL levels more effectively than use of ARB alone. These results contribute to the possibility of lowering ox-LDL levels as a means of enhancing cardiovascular protection. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Copyright of Drug Research / Arzneimittel-Forschung (Editio Cantor Verlag fur Medizin und Naturwissenschaften) is the property of Editio Cantor Verlag fur Medizin und Naturwissenschaften and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The effects of verapamil on the large conductance Ca-activated K (BK) channel from rat aortic smooth muscle cells were examined at the single channel level. Micromolar concentrations of verapamil produced a reversible flickering block of the BK channel activity. Kinetic analysis showed that verapamil decreased markedly the time constants of the open states, without any significant change in the time constants of the closed states. The appearance of an additional closed state-specifically, a nonconducting, open-blocked state--was also observed, whose time constant would reflect the mean residence time of verapamil on the channel. These observations are indicative of a state-dependent, open-channel block mechanism. Dedicated kinetic (group) analysis confirmed the state-dependent block exerted by verapamil. D600 (gallopamil), the methoxy derivative of verapamil, was also tested and found to exert a similar type of block, but with a higher affinity than verapamil. The permanently charged and membrane impermeant verapamil analogue D890 was used to address other important features of verapamil block, such as the sidedness of action and the location of the binding site on the channel protein. D890 induced a flickering block of BK channels similar to that observed with verapamil only when applied to the internal side of the membrane, indicating that D890 binds to a site accessible from the cytoplasmic side. Finally, the voltage dependence of D890 block was assessed. The experimental data fitted with a Langmuir equation incorporating the Woodhull model for charged blockers confirms that the D890-binding site is accessed from the internal mouth of the BK channel, and locates it approximately 40% of the membrane voltage drop along the permeation pathway. [ABSTRACT FROM AUTHOR]