Valsartan

The organotin(IV) compounds used in chemotherapy due to its lipophilicity, affected by the number of carbon atoms and the cytotoxicity. These are affected by the obtainability of Sn coordination bond and bond stabilization between ligand and tin. Two novel organotin(IV) complexes were synthesized, characterized, and tested against human lung cancer cells (A549). The cytotoxic effect of the prepared organotin(IV) complexes against human lung cancer cells (A549) was investigated using the MTT colorimetric assay. Apoptosis was investigated by flow cytometry. The cytotoxicity assay reveals that the Bu 2 SnL 2 complex is more active to inhibit the growth of A549 cells compared to the Ph 2 SnL 2 , and doxorubicin, nevertheless at high concentration (50 and 100) µg/mL the doxorubicin was more affective to inhibit the viability of A549 cells.

A simple, accurate, specific and precise UV Spectrophotometric method has been developed for estimation of valsartan in pure and pharmaceutical formulation. The λmax of valsartan in methanol and water was found to be 248.21 nm. Methanol and water is used as diluent in equal proportion. The drug exhibited the linearity in the concentration range of 2-20μg/ml with correlation coefficient of 0.999. The % recovery of the drug for the proposed was found to be 99.2%. The limit of detection and limit of quantification was found to be 0.15% and 0.45% respectively. No interference was observed in the presence of common pharmaceutical excipient. The method was validated as per ICH guidelines. The developed method was successfully employed for the estimation of valsartan in pharmaceutical dosage form.

In the present study, design of oral immediate release tablets of Valsartan by direct compression technique was carried out. The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV'S) in different ratios. The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated by using microcrystalline cellulose (diluents), potato starch, acacia (binder) and magnesium stearate (lubricant). The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. The In-vitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

A  simple,  robust,  precise  HPLC  method  was  developed  and  the
method  has  been  validated  for  the  estimation  of  valsartan  and
nebivolol  simultaneously  in  its  combined  dosage  forms  as  well  as
individual formulations. Both the compounds are well resolved in a
isocratic  method  by  using  the  mobile  phase  composition  of
acetonitrile: methanol: pH4.0 0.02M Potassium hydrogen phosphate
buffer in the ratio of 50:20:30 v/v at a flow rate of 1.0mL/min using a
C-18 column. The detection was carried out at 210nm.. The retention
time  of  Nebivolol  and  Valsartan  were  2.5  min  and  4.3  min
respectively.  The  developed  method  was  validated  for  specificity,
linearity,  precision,  accuracy,  limit  of  detection  (LOD),  limit  of
quantification (LOQ) and robustness as per ICH guidelines. Linearity
for Nebivolol and Valsartan were found in the range of 48-112 µg/ml
and  3.0-7.0  µg/ml,  respectively.  The  percentage  recoveries  for
Nebivolol  and  Valsartan  ranged  from  98.9-100.8  %  and  98.9-101.1
%,  respectively.  The  proposed  method  could  be  used  for  routine
analysis of Nebivolol and Valsartan in their combined dosage forms

Simple and rapid assay method is primary prerequisite in quality assurance department for any pharmaceutical dosage form. When two drugs are combined in a single dosage form, it becomes difficult to estimate them simultaneously with required accuracy and precision. Here we have proposed a simple and rapid UV spectrophotometric assay method for simultaneous determination of amlodipine besylate and valsartan in both bulk drug and commercial dosage forms. Method employed was Zero absorbance method where amlodipine and valsartan were determined at 363 nm and 290 nm respectively. At 363 nm valsartan don't have absorption and at 290 nm amlodipine has zero absorption. Linearity was established at 8 µg/mL -80 µg/mL for amlodipine (y= 0.012X + 0.002 R 2 = 0.999) and 4 µg/mL -300 µg/ml for Vasartan (y= 0.002X + 0.017 R 2 = 0.999). Method was found to be accurate and precise with %RSD<2 for all the validation parameters employed. Method was found to be very sensitive with LOD 2.4 µg/mL and 3.6 µg/mL whereas LOQ was 7.5 µg/mL and 11 µg/mL for Amlodipine besylate and Valsartan respectively. As method uses methanol as a solvent to dissolve, it is cost effective for routine analysis in quality assurance department for determination of these drugs individually or simultaneously.

The present study has a design to evaluate the valsartan conventional tablets by using various binders like acacia, sucrose, starch, gelatin, hydroxypropyl methylcellulose (HPMC), and polyvinyl-pyrrolidone (PVP). Employing the above selected six binding agents, valsartan tablets were prepared by wet granulation technique. The prepared granules were evaluated for their physic-chemical characteristics. The prepared tablets also evaluated for post-compression parameters like drug content, hardness, friability, and disintegration time and dissolution rate.The prepared valsartan tablets follow zero order kinetics. Formulation F2 showed better dissolution rate (89.37%) among all the formulations along with lowest disintegration time(2.5 minutes),which contains sucrose as a binding agent. From the ANOVA study, it was observed that there is a significant differencein the dissolution rate among the formulations. So F2 formulation is considered as optimized formulation.

The present study describes development and validation of simple, rapid, sensitive and stability indicating highperformance liquid chromatographic assay method for simultaneous determination of Amlodipine besylate and Valsartan in bulk as well as in commercial formulation. Analytical separation was achieved with RP Waters Symmetry C18 Column [150×4.6 mm] using a combination of methanol and potassium dihydrogen phosphate buffer [0.01 M] pH 2.5, in ratio 60:40 v/v with flow rate of 1 mL min −1 . The retention times for Amlodipine and Valsartan were found to be 4.6 and 7.6 min respectively. Both the drugs were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions individually as well as in combination, subsequently samples were analyzed by the proposed method. Detection was done by PDA detector at 238 nm. Method was found to be very sensitive as LOD found to be 20 ng/mL and 44 ng/mL for Amlodipine besylate and Valsartan respectively. The method was found to be specific and stability indicating as no interfering peaks of degradation compounds and excipients were noticed. The developed method was validated with respect to linearity, accuracy, precision, specificity, robustness as per International Conference on Harmonization (ICH) guidelines. The proposed method hence useful for the application in quality control laboratories for quantitative analysis of both the drug individually or in combination, as it is simple and rapid method with excellent accuracy and precision.

Valsartan is a BCS class II antihypertensive drug whose bioavailability is dissolution rate limited. Various capsule formulations of valsartan were prepared using micro crystalline cellulose and sodium lauryl sulfate. Their dissolution profiles were compared with commercial marketed formulations. Formulation J was found to have similar t 90 values to marketed brands statistically. Influence of sodium lauryl sulfate on the solubility of valsartan was studied and was found to increase with the concentration of sodium lauryl sulfate. Compatibility of valsartan with micro crystalline cellulose and sodium lauryl sulfate was studied by non-thermal methods like HPLC and IR.

Abstract: Despite significant advances in pharmacologic approaches to treat hypertension during the last decades, hypertension- and hypertension-related organ damage are still a high health and economic burden because a large proportion of patients with hypertension do not achieve optimal blood pressure control.

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Integrando los inhibidores de neprilisina y receptores de angiotensina a los distintos escenarios de la insuficiencia cardíaca.
Los progresos en el tratamiento de la insuficiencia cardíaca (IC) son continuos, pese a lo cual la enfermedad permanece como uno de los principales desafíos de la cardiología debido tanto a su prevalencia como a su decepcionante pronóstico. Se trata de un síndrome con formas clínicas heterogéneas y mecanismos fisiopatológicos
diferentes que condicionan una estrategia de abordaje compleja.
La Federación Argentina de Cardiología y la Sociedad Argentina de Cardiología han considerado necesario establecer en conjunto, lineamientos de cómo abordar el uso de ARNI en los diferentes escenarios del continuo de la IC. Estas recomendaciones no pretenden reemplazar a las actuales guías disponibles del tema, sino a partir
de la evidencia disponible aportar una toma de posición basada en el juicio crítico para colaborar en las decisiones frente al paciente.
Tras varios años de estancamiento en los progresos terapéuticos, a partir del estudio PARADIGM-HF en el año 2014 con sacubitrilo/valsartán (S/V), nuevas alternativas superadoras generaron gran expectativa pero también la necesidad de definir cómo implementarlas ante las múltiples situaciones clínicas que la enfermedad plantea.1
El presente documento está básicamente dividido en dos secciones. En la primera se plantean los diferentes escenarios clínicos que propone la IC, con el objeto de definir cuál es la mejor estrategia terapéutica en cada uno de ellos. (Figura 1) Se toman en cuenta la presentación clínica de acuerdo con el estadio y la clase funcional, la fracción de eyección y la consecuente estratificación de la IC, y la comprensión dinámica de fases recurrentes: ambulatorio-hospitalizado, que implican diferencias en los tratamientos, pero siempre orientados a la etapa posterior
(prevenir la descompensación y la re-hospitalización). Una parte de esta sección está dedicada a analizar diferentes aspectos que condicionan el tratamiento y no deben soslayarse en el paciente individual: comorbilidades, estado de fragilidad, vinculación con otras enfermedades coexistentes, circunstancias que demandan plasticidad para adaptar los recursos terapéuticos a las posibilidades concretas a fin de individualizar el mejor tratamiento posible.

This article deals with the results of in vitro interactions among glimepiride, ciprofloxacin HCl and valsartan at the molar ratio of 1:1:1 by DSC and HPLC method. The DSC thermogram of the mixture (glimepiride, ciprofloxacin HCl and valsartan) showed different melting endotherm than the melting endotherm for standard valsartan, ciprofloxacin HCl and glimepiride. Since the melting endotherms of mixture and individual drugs were not identical, it demonstrated the presence of interactions among the drugs. This result was further verified by HPLC to observe their recovery range. The % recovery ranges were found as 25.33, 23.49 and 135.82% for glimepiride, ciprofloxacin HCl and valsartan, respectively. The abnormal percentage recovery range and peak areas fluctuation further indicated the interactions among glimepiride, ciprofloxacin HCl and valsartan.

Aim Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the degree of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI. Methods and Results C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of regional contraction in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contraction were preserved.

The purpose of present study was to develop chemically cross-linked poly vinyl alcohol-copoly
(acrylic acid) hydrogel (PVA-AA hydrogel) for pH-responsive and controlled delivery of valsartan.
Hydrogels were synthesized using free radical polymerization technique. Polymer (PVA) was chemically
cross-linked with monomer (acrylic acid) in aqueous medium. Ethylene glycol di-methacrylate (EGDMA)
and benzoyl peroxide (BPO) were used as cross-linker and initiator, respectively. Drug loading was performed
with valsartan as a model drug. Characterization of hydrogels was performed by SEM, FT-IR,
XRD, TGA and DSC. Hydrogels were evaluated for pH responsive behavior by equilibrium swelling ratio
and swelling dynamics at low and high pH. Formation of hydrogel was confirmed by FT-IR, XRD, TGA
and DSC studies. Maximum swelling, drug loading and release has been observed at pH 7.4. It is concluded
that highly stable PVA and AA based polymeric matrices are developed, which are highly pH-sensitive.
These polymeric matrices have potential to be used as a carrier for controlled delivery of valsartan.
RESUMEN. El propósito de este estudio fue desarrollar químicamente un hidrogel reticulado de polivinilo alcohol-
co-poliácido acrílico (hidrogel de PVA-AA) para obtener una respuesta de valsartán sensible y controlada al
pH. Los hidrogeles fueron sintetizados utilizando la técnica de polimerización por radicales libres. El polímero
(PVA) fue químicamente reticulado con un monómero (ácido acrílico) en medio acuoso. Etilenglicol di-metacrilato
(EGDMA) y peróxido de benzoilo (BPO) se utilizaron como agente de reticulación e iniciador, respectivamente.
La carga de fármacos se realizó con valsartán como un fármaco modelo. La caracterización de los hidrogeles
se realizó por SEM, FT-IR, XRD, DSC y TGA. Los hidrogeles fueron evaluados para el comportamiento
de respuesta al pH por la relación de hinchamiento de equilibrio y de hinchamiento dinámico a pH bajo y alto. La
formación del hidrogel se confirmó por FT-IR, XRD, TGA y los estudios de DSC. El máximo hinchamiento, carga
de fármaco y liberación se observó a pH 7,4. En conclusión, se desarrollaron matrices poliméricas de PVA altamente
estables basados en AA que son altamente sensible al pH. Estas matrices poliméricas pueden ser potencialmente
útilies como portadores para la liberación controlada de valsartán.

Failure to decrease blood pressure (BP) during the night is associated with higher cardiovascular (CV) morbidity and mortality. There is strong evidence that fixed-dose combinations (FDCs) of antihypertensive agents are associated with significant improvement and non-significant adverse effects. The aim of the present study was to evaluate whether FDC affected nocturnal BP favorably in patients with uncontrolled, non-dipper hypertension (HT). All non-dipper hypertensives were either newly diagnosed with stage 2-3 HT or had HT uncontrolled with monotherapy. Patients (n=195) were consecutively assigned to 4 treatment groups: FDC of valsartan/amlodipine (160/5 mg), free-drug combination of valsartan 160 mg and amlodipine 5 mg, amlodipine 10 mg, and valsartan 320 mg. Ambulatory blood pressure monitoring (ABPM) was repeated at 4th and 8th week. Average 24-h (24-hour) and nocturnal BP were similar among the groups at baseline evaluation, and had significantly decreased by the fourth week ...

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and −dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorub...

The enhancement of aqueous solubility, physicochemical and micromeritics properties of poorly soluble drugs is of major concern
in pharmaceutical formulation industries. It is observed in the drug industry that on average more than 1/3 of newly drugs are poorly water-soluble. Poor “drug like” properties of lead compounds lead to ineffective absorption from the site of administration, less bioavailability which has been designated as an important part of the high clinical failure. In the present work, Valsartan, nonpeptide, orally active and specific angiotensin II antagonist acting on the AT1 receptor subtype belongs to BCS class II drug (highly permeable and low soluble) is used as lead compound. A simultaneous DSC, FT-IR, SEM, XRPD micro spectroscopy, dissolution study and micromeritics properties studies was used to quickly investigate the Co-Crystal. Tablet formulation was developed by direct compression method and there evaluation was performed.

In the present study, design of oral immediate release tablets of Valsartan by direct compression technique was carried out. The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV'S) in different ratios. The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated by using microcrystalline cellulose (diluents), potato starch, acacia (binder) and magnesium stearate (lubricant). The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. The In-vitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

Conclusion: Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated.

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Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin-and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Background: Many factors were blamed for the worse prognosis in COVID-19. Heart failure patients are thought to be under increased risk because of either immune-compromised basal status or possible interaction of viral infection with ongoing medications, such as the Renin-Angiotensin-Aldosterone system (RAAS) blockers. Sacubitril is a neprilysin inhibitor and its' combination with valsartan is recommended as a novel medication for heart failure. Case Report: A 71 years of age female with end-stage heart failure was hospitalized for COVID-19 pneumonia. She was under sacubitril/valsartan combination for the heart failure, and at the end of the first week of hospitalization, clinical and laboratory parameters recovered uneventfully. Sacubitril/valsartan therapy was continued without complications during the in-hospital course. Conclusion: Specific therapies for heart failure should not be withdrawn in COVID-19. To our knowledge, this is the first case report documenting the clinical progress of a COVID-19 pneumonia patient who was already under sacubitril/valsartan treatment.

Valsartan is a specific angiotensin II antagonist used for the treatment of hypertension. It suffers from low aqueous solubility and high variability in its absorption after oral administration. The aim of this study was to improve the dissolution and thereby the bioavailability of Valsartan through the development of self nano-emulsifying drug delivery systems. Four ternary phase diagrams were constructed to identify the self-emulsification region of Capmul® MCM, Labrafil® M1944, Capryol™ 90 and Labrafac® PG together with Cremophore® RH 40 and Transcutol™ HP as oil, surfactant and co-surfactant, respectively. The effect of oil type, oil and surfactant concentration on droplet size and in vitro Valsartan dissolution were studied. The protective effect of the optimum formula F5 in adrenaline-induced oxidative stress in rats during myocardial infarction was determined. Formula F5 exhibited globule size of (13.95 nm) with 76.07% ± 1.10 of Valsartan dissolved after five minutes compared...

Recent studies demonstrated that the antihypertensive drug Valsartan improved spatial and episodic memory in mouse models of Alzheimer's Disease (AD) and human subjects with hypertension. However, the molecular mechanism by which Valsartan can regulate cognitive function is still unknown. Here, we investigated the effect of Valsartan on dendritic spine formation in primary hippocampal neurons, which is correlated with learning and memory. Interestingly, we found that Valsartan promotes spinogenesis in developing and mature neurons. In addition, we found that Valsartan increases the puncta number of PSD-95 and trends toward an increase in the puncta number of synaptophysin. Moreover, Valsartan increased the cell surface levels of AMPA receptors and selectively altered the levels of spinogenesis-related proteins, including CaMKII and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling.

Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with high-fat diet. Treatment with saturated fatty acid palmitic acid (PA) (0.8mM) for 24h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone BiP and proapoptotic transcription factor CHOP protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of IRE1α, phosphorylated eIF2α and ATF4 as well as activation of caspase 3. PA treatment was associated with increased angiotensin II levels in cultured medium. The AT1R blocker...

The main barrier for transdermal delivery is the obstacle property of the stratum corneum. Many types of chemical penetration enhancers have been used to breach the skin barrier; among the penetration enhancers, terpenes are found as the most highly advanced, safe, and proven category. In the present investigation, the terpenes anethole, menthone, and eugenol were used to enhance the permeation of valsartan through rat skin in vitro and their enhancement mechanism was investigated. Skin permeation studies of valsartan across rat skin in the absence and the presence of terpenes at 1% w/v, 3% w/v, and 5% w/v in vehicle were carried out using the transdermal diffusion cell sampling system across rat skin and samples were withdrawn from the receptor compartment at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h and analysed for drug content by the HPLC method. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FTI...

To address global warming through carbon dioxide storage, three valsartan metal complexes were synthesized in excellent yields (87-92%) through a reaction of the appropriate metal chloride (tin chloride, nickel chloride hexahydrate, or magnesium chloride hexahydrate) and excess valsartan (two mole equivalents) in boiling methanol for 3 h. The structures of the metal complexes were established based on the data obtained from ultraviolet-visible, Fourier transform infrared, and proton nuclear magnetic resonance spectra, as well as from elemental analysis, energy-dispersive X-ray spectra, and magnetic susceptibility. The agglomeration and shape of the particles were determined using field emission scanning electron microscopy analysis. The surface area (16.63-22.75 m 2 /g) of the metal complexes was measured using the Brunauer-Emmett-Teller method, whereas the Barrett-Joyner-Halenda method was used to determine the particle pore size (0.011-0.108 cm 3 /g), total average pore volume (6.50-12.46 nm), and pore diameter (6.50-12.47 nm), for the metal complexes. The carbon dioxide uptake of the synthesized complexes, at 323 K and 4 MPa (40 bar), ranged from 24.11 to 34.51 cm 2 /g, and the nickel complex was found to be the most effective sorbent for carbon dioxide storage.

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and −dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorub...

Failure to decrease blood pressure (BP) during the night is associated with higher cardiovascular (CV) morbidity and mortality. There is strong evidence that fixed-dose combinations (FDCs) of antihypertensive agents are associated with significant improvement and non-significant adverse effects. The aim of the present study was to evaluate whether FDC affected nocturnal BP favorably in patients with uncontrolled, non-dipper hypertension (HT). All non-dipper hypertensives were either newly diagnosed with stage 2-3 HT or had HT uncontrolled with monotherapy. Patients (n=195) were consecutively assigned to 4 treatment groups: FDC of valsartan/amlodipine (160/5 mg), free-drug combination of valsartan 160 mg and amlodipine 5 mg, amlodipine 10 mg, and valsartan 320 mg. Ambulatory blood pressure monitoring (ABPM) was repeated at 4th and 8th week. Average 24-h (24-hour) and nocturnal BP were similar among the groups at baseline evaluation, and had significantly decreased by the fourth week ...

Context: The angiotensinogen (AGT) G-217A polymorphism has been proved as one factor contributing the susceptibility of hypertension, meanwhile, the effect of this polymorphism to the variability antihypertensive response remains unknown. Aims: To investigate whether the angiotensinogen (AGT) G-217A polymorphism affects the blood pressure response to telmisartan and valsartan in Indonesian hypertensive patients. Methods: The blood pressure was measured by ambulatory blood pressure monitoring (ABPM) and plasma angiotensinogen (AGT) levels of telmisartan-and valsartan-treated AGT G-217A polymorphism hypertensive patients (n=46) were analyzed using ELISA at the baseline and 4 months after treatments. Molecular docking was used to predict the interaction between C/EBPα and AGT G-217A polymorphism. Results: Daytime and 24 hours blood pressure in telmisartan-treated-217 AA/AG patients were significantly lower compared to GG genotype patients. The plasma AGT level in those who had AA/AG genotype and received telmisartan 80 mg was also slightly decreased compared to GG genotype, even these differences were failed to reach statistically significant. The docking results showed that the basic region of C/EBPα transcription factor recognized the partially homologous of its consensus sequences within-217A oligonucleotide, but not in-217G oligonucleotide. Conclusions: The blood pressure reduction responses in telmisartan-treated angiotensinogen G-217A polymorphism hypertensive patients might correlate with PPARγ agonist effects of telmisartan via C/EBPα and AGT -217A interaction.

Background: The complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE). Design and methods: The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke. Trial status: From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing. Conclusion: The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries.

Increases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection fraction, and pilot data suggest potential benefit in heart failure with preserved ejection fraction (HFpEF).

The effects of levosimendan on cerebrovascular lesions and mortality were investigated in models of primary and secondary stroke. We aimed to determine whether the effects of levosimendan are comparable to and/or cumulative with those of valsartan, and to investigate whether levosimendan-induced vasodilation has a role in its effects on stroke. In a primary stroke Dahl/Rapp rat model, mortality rates were 70% and 5% for vehicle and levosimendan, respectively. Both stroke incidence (85% vs. 10%, P <0.001) and stroke-associated behavioral deficits (7-point neuroscore: 4.59 vs. 5.96, P <0.001) were worse for vehicle compared to levosimendan. In a secondary stroke model in which levosimendan treatment was started after cerebrovascular incidences were already detected, mean survival times were 15 days with vehicle, 20 days with levosimendan (P = 0.025, vs. vehicle), 22 days with valsartan (P = 0.001, vs. vehicle), and 31 days with levosimendan plus valsartan (P <0.001, vs. vehicle). The respective survivals were 0%, 16%, 20% and 59%, and the respective incidences of severe lesions were 50%, 67%, 50% and 11%. In this rat model, levosimendan increased blood volume of the cerebral vessels, with significant effects in the microvessels of the cortex (¨R = 3.5 ±0.15 vs. 2.7 ±0.17 ml for vehicle; P = 0.001) and hemisphere (¨R = 3.2 ±0.23 vs. 2.6 ±0.14 ml for vehicle; P = 0.018). Overall, levosimendan significantly reduced stroke-induced mortality and morbidity, both alone and with valsartan, with apparent cumulative effects, an activity in which the vasodilatory effects of levosimendan have a role.

Conclusion: This large, multiethnic study supports the evidence that Aml/Val and Aml/Val/HCT single-pill combinations are effective in diverse and clinically important subgroups of patients with hypertension.

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