Losartan

Proteinuric diabetic kidney disease frequently progresses to ESRD. Control of BP delays progression, but the optimal BP to improve outcomes remains unclear. The objective of this analysis was to evaluate the relationship between BP and renal outcomes in proteinuric diabetic kidney disease. BP data from all 1448 randomized participants in the Veterans Affairs Nephropathy in Diabetes Trial were included in a post hoc analysis. The associations of mean on-treatment BP with the primary end point (decline in eGFR, ESRD, or death), renal end point (decline in eGFR or ESRD), rate of eGFR decline, and mortality were measured. The median (25th, 75th percentile) follow-up time was 2.2 (1.2, 3.0) years. There were 284 primary end points. In univariate analyses, both mean systolic and mean diastolic BPs were strongly associated (P<0.001) with the primary end point. After multivariate adjustment, the hazard of developing the primary end point became progressively higher as mean systolic BP ro...

Hypertension is associated with cerebrovascular remodeling and endothelial dysfunction, which may reduce cerebral vasomotor reactivity to CO2. Treatment combining blood pressure (BP) reduction with inhibition of vascular effects of angiotensin II may reverse these changes. However, the reduction in BP at the onset of treatment can compromise cerebral perfusion and exhaust vasomotor reserve, leading to impaired CO2 reactivity. Eleven patients (nine men, two women) with newly diagnosed, untreated mild-to-moderate hypertension aged (mean (s.d.)) 52 (9) years, and eight controls (seven men, one woman) aged 46 (10) years were studied. Patients received losartan/hydrochlorothiazide (50/12.5 or 100/25 mg) to reduce BP to <140/<90 mm Hg within 1-2 weeks. BP (Finapres), heart rate (HR), CBFV (cerebral blood flow velocity, transcranial Doppler), cerebrovascular resistance, and CO2 reactivity were measured at baseline, after the rapid BP reduction, and after long-term treatment (3-4 mont...

Biotransformation potential of a thermophilic fungal strain Rhizomucor pusillus NRRL 28626 was investigated using anti-hypertension drug losartan as a model drug in order to find the metabolic similarities of this fungus with that of mammals. Five metabolites viz. M1, M2, M3, M4, and M5 were detected at pH 6.0 and temp of 45ºC during four days incubation. The metabolites were detected by high-performance liquid chromatography (HPLC) and the structures were elucidated by liquid chromatography- tandem mass spectrometry (LC-MS/MS) analysis as glucuronic acid compound (M1), 3-hydroxy-N-acetyl losartan (M2), N-acetylated carboxylic acid metabolite of losartan (M4), and two novel metabolites M3 and M5. The metabolites of losartan produced were by glucuronidation, hydroxylation, acylation, dealkylation, dechlorination, and oxidation which clearly reveals that R.pusillus exhibits wide reaction diversity.

Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6-9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the stu...

Context: The validation of a method is synonymous with the quality of the obtained results. The dissolution test is an analytical technique to evaluate the quality and stability of drugs during their development.

Aims: To evaluate whether the UV spectrophotometric method for the quantification of losartan potassium in tablets from the dissolution test at pH 1.2, 4.5 and 6.8 meet with the validation parameters.

Methods: The determination and evaluation of validation parameters were carried out under the guidelines of the regulatory entities. Linearity and range, accuracy, precision, specificity, limits of detection and quantification, robustness, stability of the sample solution were evaluated, and the filter test was added. All data obtained were subject to an analysis of variance and t-student analysis with a confidence level of 95% (α = 0.05).

Results: The UV spectrophotometric method meets the acceptance criteria for each validation parameter. Likewise, it was identified that the prepared solutions were stable at pH 6.8 for 24 hours; however, they were not stable at pH 1.2 and 4.5.

Conclusions: The method meets with the validation criteria and is suitable to be used for quantifying samples obtained from the losartan potassium tablet dissolution test.

The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG II receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance.

Dyslipidaemia is associated with high risk for cardiovascular disease and lipid management is arguably necessary, especially in hypertensive subjects. There is an implication that angiotensin receptor blockers (ARB) are characterised by a beneficial effect on lipid profile in addition to their blood pressure lowering properties. This study was conducted to evaluate blood pressure control and the plasma lipid profile in hypertensive patients after six months' treatment with ARB. We studied 2438 consecutive, untreated patients with uncomplicated essential hypertension (mean blood pressure [BP] 167/100 mmHg). All patients underwent full lab and echo examination at drug-free baseline, which was repeated after at least 6 months of ARB monotherapy. Overall, ARB treatment reduced BP levels significantly (p<0.0001). Evaluating lipid profile changes, a significant (p<0.0001) reduction was noted in total cholesterol (TC: from 220 +/- 39 to 216 +/- 36 mg/dL), low density lipoprotein ...

The renin–angiotensin–aldosterone-system (RAAS) is an important regulator of blood pressure and fluid-electrolyte homeostasis. RAAS has been implicated in pathogenesis of hypertension, congestive heart failure, and chronic renal failure. Aliskiren is the first non-peptide orally active renin inhibitor approved by FDA. Angiotensin Converting Enzyme (ACE) Inhibitors are associated with frequent side effects such as cough and angio-oedema. Recently, the role of ACE2 and neutral endopeptidase (NEP) in the formation of an important active metabolite/mediator of RAAS, ang 1–7, has initiated attempts towards development of ACE2 inhibitors and combined ACE/NEP inhibitors. Furukawa and colleagues developed a series of low molecular weight nonpeptide imidazole analogues that possess weak but selective, competitive AT1 receptor blocking property. Till date, many compounds have exhibited promising AT1 blocking activity which cause a more complete RAAS blockade than ACE inhibitors. Many have reached the market for alternative treatment of hypertension, heart failure and diabetic nephropathy in ACE inhibitor intolerant patients and still more are waiting in the queue. But, the hallmark of this area of drug research is marked by a progress in understanding molecular interaction of these blockers at the AT1 receptor and unraveling the enigmatic influence of AT2 receptors on growth/anti-growth, differentiation and the regeneration of neuronal tissue. Different modeling strategies are underway to develop tailor made molecules with the best of properties like Dual Action (Angiotensin And Endothelin) Receptor Antagonists (DARA), ACE/NEP inhibitors, triple inhibitors, AT2 agonists, AT1/TxA2 antagonists, balanced AT1/AT2 antagonists, and nonpeptide renin inhibitors. This abstract gives an overview of these various angiotensin receptor antagonists.

The Literature survey indicates several methods for the determination of Losartan potassium. So an attempt was made to develop and validate a simple, precise, accurate, and economical RP-HPLC method as per ICH guidelines for the estimation of Losartan potassium in bulk and pharmaceutical dosage forms. A simple reverse phase HPLC method was developed for the determination of Losartan potassium present in pharmaceutical dosage forms. Hypersil Silica (250 x 4.6 mm, packed with 5μm) in an isocratic mode with mobile phase Acetonitrile: Triethylamine buffer PH3 (50:50) was used. The flow rate was 1.0ml/ min and effluent was monitored at 254 nm. The retention time was 5.1min for Losartan potassium. The linearity ranges were found to be 40-120g/ml
Keywords: losartan potassium.

Tachycardia accompanying exercise shortens the duration of diastole, reducing the time available for the left ventricular (LV) filling. Thus, the LV must fill more rapidly for the stroke volume to increase (or even be maintained) during exercise. Normally, this is accomplished without requiring an excessive increase in left atrial (LA) pressure by an acceleration of LV relaxation and a fall in LV early diastolic pressure during exercise. This response is lost following the development of heart failure due to systolic dysfunction, both in experimental animals and in patients. In fact, in such situations, LV relaxation slows and LV early diastolic pressure increases due to exercise. Thus, any diastolic dysfunction present at rest in CHF during systolic dysfunction is exacerbated during exercise. Similarly, patients with primary diastolic dysfunction heart failure with preserved systolic function may not be able to augment LV filling rates without an abnormal increase in LA pressure. T...

As arterial hypertension is the most important risk factor for ischemic stroke, the relevant guidelines recommend rigorous treatment to normalize blood pressure. Hypertension can also be associated with cognitive decline and dementia. Therefore, the effect of a long-term therapy with the AT(1) antagonist losartan (+/- hydro chloro thiazide [HCTZ]) on cognitive function in patients with essential hypertension and additional cerebrovascular risk factors was investigated. Prospective, open observational study in 6,206 adult patients with known essential hypertension and cerebrovascular risk factors (most with a 10-year stroke risk of >or= 20% based on the Framingham Score). Demographic data, blood pressure, selected laboratory parameters, and cognitive function (c.I. test) were determined at baseline and after 3, 6, and 12 months. The patients' mean age was 65.8+/-10.7 years and 46.1% of the patients were male. In addition to treatment with losartan +/- HCTZ, 54.1% of the patien...

Diabetic kidney disease is characterized by persistent albuminuria (>300 mg/dl or >200 μg/min) that is confirmed on at least 2 occasions 3 to 6 months apart, with a progressive decline in the glomerular filtration rate (GFR), elevated arterial blood pressure, and an increased ...