cozaar generic reviews
Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels.
cozaar name brand
From the patent investigation it is clear that new areas on the subject are still offered for new discoveries. New structural features can be still considered in the synthetic compounds that can advance the knowledge and beneficial effects on diseases related to Angiotensin II and AT1 receptor. There is era also for new formulations (i.e., cyclodextrins, polymers and liposomes). The multitarget approach can be further strengthened and more combinations can be sought in the rational drug design for seeking cocktails. Furthermore, the revealing of the complexity of the RAS offers new avenues for novel targets and this must not be overlooked.
cozaar 40 mg
A high-sodium diet downregulated AQP-1 and AQP-2 expression levels in the proximal tubule and collecting duct, respectively. The high-sodium diet also induced Ang II, TGF-β(1) and α-SMA overexpression and decreased eNOS expression in the renal cortex and medulla. Losartan increased the diuresis and natriuresis, favoring urinary sodium concentration. Additionally, losartan prevented the profibrogenic response, decreasing Ang II, TGF-β(1) and α-SMA levels and normalizing AQP-2 expression in the HS-L group. AQP-1 expression was upregulated by losartan in both the NS-L and HS-L groups.
cozaar y alcohol
Losartan, amlodipine, and especially fosinopril can inhibit cardiomyocyte apoptosis, prevent myocardial fibrosis, and reverse heart hypertrophy. Inhibition of myocardium rennin--angiotension--aldsteron system may be the mechanism of the three drugs' cardioprotective effects.
cozaar dose maximum
We report new examples of a series of losartan-hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan.
cozaar 60 mg
Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on betaig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-beta1 and intrarenal angiotensin II were compared across treatment groups.
cozaar double dose
Angiotensin II initiates a variety of physiological effects in the kidney by binding to high-affinity receptors on plasma membranes. Recently, two subtypes of angiotensin II receptors have been distinguished on the basis of differences in signal transduction mechanisms, binding affinity to agonists and antagonists, and inhibition of binding by dithiothreitol. To evaluate the density and distribution of these receptor subtypes in the kidney, we performed an in situ autoradiographic study on frozen tissue sections obtained from rat and human kidneys. Sections were incubated with 125I-[Sar1,Ile8]angiotensin II and binding specificity was verified by competition with unlabeled [Sar1]angiotensin II. Angiotensin II receptor subtypes were characterized by competition with the nonpeptide receptor antagonists, DuP 753 (type 1) and PD123177 (type 2). Both rat and human kidney exhibited a high concentration of angiotensin II receptors in glomeruli and in the longitudinal bands traversing the outer portion of the medulla, corresponding to the medullary vascular bundles. Binding affinity (Kd = 0.6 +/- 0.4 nM), determined in rat kidney, was similar to that reported previously in isolated glomeruli and membrane vesicles prepared from renal tubules. Angiotensin II binding was almost completely inhibited by DuP 753, whereas PD123177 had little effect. Thus the predominant angiotensin II receptor subtype in both rat and human kidney is type 1. The distribution of angiotensin II receptors correlates well with the intrarenal sites at which the peptide has its major physiological effects.
cozaar lethal dose
Co-administration of vitamin C and losartan was compared with losartan (10 mg/kg), vitamin C (250 mg/kg), and placebo in 4 groups of rats with CIN. The prophylactic agents were injected daily for a period of 4 days, and on day 3, a single dose (6 mg/kg) of cisplatin was administrated. The animals were sacrificed 7 days later for pathological examination of the kidneys.
cozaar maximum dose
Angiotensin II (Ang II) AT2 receptors were purified 40,000-fold to a nearly homogeneous state after solubilization from neonatal rat kidney membranes with 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propane-sulfonic acid. Comparable IC50 values for the soluble extract (0.32 nM) and membranes (0.31 nM) were obtained by competition curves with 125I-labeled CGP42112, a selective AT2 ligand. Binding to AT2 receptors in the soluble extract was not sensitive to dithiothreitol. AT2 receptors were further purified by gel filtration and a CGP42112 Sepharose affinity column. Ang II AT2 receptors were selectively eluted with 5 microM CGP42112 at 4 degrees C, and a single band with an apparent molecular mass of 71 kDa was obtained after SDS/PAGE. Two-dimensional electrophoresis confirmed the purity of the protein and an isoelectric point of 5.3-5.5 was obtained. A highly selective elution of the AT2 receptors from the affinity column was performed with 5 nM 125I-labeled CGP42112 at room temperature after the column was treated with 1 microM losartan in the presence of high salt. After cross-linking, a major labeled protein with similar molecular mass and isoelectric point was obtained. Dissociation of the radiolabeled protein was insensitive to losartan but was enhanced by CGP42112, PD123177, Ang II, and [Sar1]Ang II. In summary, Ang II AT2 receptors were purified by CGP42112 affinity chromatography and selective elution and retain the pharmacological specificity of particulate receptors.
cozaar drug class
2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole, potassium salt (Losartan) (previous name, DuP 753 or MK 954) is a nonpeptide angiotensin II receptor antagonist. This study was performed to investigate the ability of Losartan to inhibit the angiotensin II-induced stimulation of the phospoinositide signalling system and the angiotensin II-induced hypertrophy in aortic vascular smooth muscle cells of normotensive Wistar-Kyoto rats. 10(-7) M Losartan abolished the angiotensin II-induced formation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. 10(-6) M Losartan completely abolished the angiotensin II-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i). 10(-6) M Losartan lacked effects on the [Arg8]vasopressin-induced elevation of [Ca2+]i. In addition, 10(-6) M completely inhibited the angiotensin II-induced stimulation of Na+/H+ exchange in the vascular smooth muscle cells. 10(-10) to 10(-6) M Losartan inhibited the angiotensin II-induced cell protein synthesis in a concentration-dependent manner, yielding to an effective concentration (ED50) of 6.2 +/- 1.8 x 10(-8) M (n = 4). Losartan did not affect the platelet-derived growth factor-BB-induced increase in cell protein. These results show that Losartan is a highly specific angiotensin II receptor antagonist which inhibits angiotensin II-induced cell growth and thus may have beneficial effects on the development and regression of vascular hypertrophy.
cozaar normal dose
Heart failure is associated with impairment in nitric oxide (NO) mediated vasodilatation, which has been demonstrated to result from a reduction in the relative expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. Further, captopril preserves normal LZ+ MYPT1 expression, the sensitivity to cGMP-mediated vasodilatation and modulates the expression of genes in the p42/44 MAPK and p38 MAPK signaling cascades. This study tests whether angiotensin receptor blockade (ARB) with losartan decreases p42/44 MAPK or p38 MAPK signaling and preserves LZ+ MYPT1 expression in a rat infarct model of heart failure. In aortic smooth muscle, p42/44 MAPK activation increases and LZ+ MYPT1 expression falls after LAD ligation. Losartan treatment decreases the activation of p42/44 MAPK to the uninfarcted control level and preserves normal LZ+ MYPT1 expression. The expression and activation of p38 MAPK, however, is low and does not change following LAD ligation or with losartan therapy. These data suggest that either reducing or blocking the effects of circulating angiotensin II, both decreases the activation of the p42/44 MAPK signaling cascade and preserves LZ+ MYPT1 expression. Thus, the ability of ACE-inhibitors and ARBs to modulate the vascular phenotype, to preserve normal flow mediated vasodilatation may explain the beneficial effects of these drugs compared to other forms of afterload reduction in the treatment of heart failure.
cozaar dosage strengths
Angiotensin II (AngII) is a main mediator in the regulation of vascular tone. Although its effects on vascular smooth muscle cells are well known, data on its role on endothelial biology are still insufficient. The present study examined the effect of endogenous and exogenous AngII on bovine aortic endothelial cells possessing both AT-1 and AT-2 receptors. A DNA synthesis-promoting effect of AT-2 blockade by PD123319 (10(-9) to 10(-7) M) was demonstrated. This effect was transduced through an AT-1-mediated pathway, as shown by using the AT-1 antagonist, losartan. In addition, an AT-1-mediated effect of AngII was demonstrated on bovine aortic endothelial cell proliferation, which occurred despite the absence of AngII-induced Ca2+ transients. In summary, the present study disclosed relevant characteristics of the effect of AngII on endothelial cell growth that have potential pathophysiologic projections, particularly for the use of selective AngII blocking agents.
cozaar normal dosage
The effects of the angiotensin II (ANG II) AT2 ligand PD 123319 and the AT1 antagonist losartan on cerebral blood flow (CBF) were studied during hemorrhagic hypotension in anesthetized rats using laser-Doppler flowmetry. In the control group CBF remained stable when mean arterial blood pressure (MABP) was lowered from 84 mmHg (baseline) to 45 mmHg, whereafter there was a pressure dependent decrease in CBF indicating inadequacy of autoregulation. Cerebrovascular resistance (CVR) was reduced until MABP 40 mmHg, where a maximum dilation was reached. PD 123319 dose-dependently (3-30 mg/kg i.v.) increased CVR through all blood pressures. Losartan 3 mg/kg i.v. had an effect similar to PD 123319. Selective stimulation of AT2 receptors with intravenous ANG II infusion, in the presence of AT1 receptor blockade by losartan, also increased CVR. As a result, reduced CBF was seen in the treatment groups. The effects of ANG II and PD 123319 30 mg/kg were antagonized by the nonselective ANG II antagonist Sar1,Ile8-ANG II (4 micrograms/kg/min i.v.). None of the treatments affected baseline CBF. The results confirm that ANG II contributes to cerebrovascular resistance and participates in the regulation of CBF apparently through AT2 receptors.
cozaar overdose symptoms
51 patients with nonalcoholic steatohepatitis (NASH) were included in an open randomized prospective comparative study with no control. Patients were divided into 2 groups depending on the chosen treatment strategy. Group 1 (n = 25) had been receiving standard treatment of NASH (Ursodeoxycholic acid 15 mg/kg once a day, per os divided into 3 doses, Atorvastatin 20 mg per os at night, Vitamin E 800 IU/day per os for 12 months); Group 2 (n = 26) had been receiving losartan 50 mg/day per os for 12 months in addition to the above mentioned standard treatment of NASH.
cozaar hctz dose
Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction patterns indicated differences in the crystal packing of the two forms. The vibrational data from infrared and Raman spectroscopy suggested a subtle change in molecular conformation and crystal packing in the two forms. Solid-state 13C NMR data of the polymorphs concurred with the vibrational data and indicated that, while the observed line widths reflect no major changes in crystallinity, signal multiplicities and chemical shifts do reflect differences in molecular packing in the respective unit cells. Thus, in the absence of crystallographic data, useful structural information could be derived from spectroscopic results to identify each of the crystalline forms.
cozaar generic name
Losartan alleviates bleomycin-induced pulmonary fibrosis in rats. Inhibiting the expressions of MCP-1 and bFGF in lung tissues may be one of the mechanisms.
cozaar medication generic
Eplerenone is a selective aldosterone blocker that effectively lowers BP in both white and black patients with hypertension and provides meaningful further antihypertensive efficacy when added to patients whose hypertension is inadequately controlled by angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.
cozaar 150 mg
Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study.
cozaar missed dose
We think that losartan should be recommended to use for protection against atherosclerosis at the young aged individuals that have multiple risks for atherosclerosis, other than hypertension.
cozaar and alcohol
Previous studies from our laboratory have shown that the cardiac sympathetic afferent reflex is enhanced in dogs with experimental heart failure. The aim of the present study was to determine if the central gain of the cardiac sympathetic afferent reflex was also enhanced in dogs with heart failure. Fifteen dogs with pacing-induced heart failure were used in this study. Seventeen sham-operated dogs served as control. At the time of the acute experiment the dogs were anesthetized with alpha-chloralose. Arterial blood pressure, heart rate, and renal sympathetic nerve activity were recorded. After sinoaortic denervation and cervical vagotomy, a thoracotomy was performed in the second intercostal space. The left stellate ganglion was identified, and the left cardiac sympathetic nerves were cut. The central end of the left cardiac sympathetic nerves was placed on bipolar stimulating electrodes. The renal sympathetic nerve activity responses to electrical stimulation (30 Hz, 1 ms with varying voltages from 1 to 10 V; or 10 V, 1 ms with varying frequencies from 1 to 30 Hz) of the afferent cardiac sympathetic nerves were compared between sham and heart failure groups. Reflex renal sympathetic nerve activity responses to stimulation of the cardiac sympathetic nerves were significantly greater in the heart failure group compared with that in the sham group (21.4 +/- 3.2 vs. 9.8 +/- 2.9% at 10 V, 30 Hz and 27.7 +/- 4.5 vs. 9.9 +/- 3.4% at 30 Hz, 10 V, heart failure vs. sham group, respectively; for both relationships, P < 0.05). This enhanced central gain of the cardiac sympathetic afferent reflex in the heart failure group was significantly attenuated after intravenous and cerebroventricular injection of the angiotensin II receptor antagonist losartan (5 mg/kg i.v. and 0.125 mg/kg in 0.1 ml i.c.v.). These data suggest that the central gain of the cardiac sympathetic afferent reflex is enhanced in dogs with heart failure and central angiotensin II plays an important role in this enhanced response.
cozaar low dose
Angiotensin receptor blockers (ARBs) have a pharmacological role in the treatment of heart failure through their blockade of the effects of angiotensin II. ARBs, however, lack the potential benefits of inhibiting the breakdown of bradykinin that is seen with ACE-Is. Historically, the medical literature assessing ARBs in the treatment of chronic heart failure have been short in duration and primarily focused on surrogate markers of disease severity. Recent, well-designed clinical trials have shed new light on the potential roles of ARBs in the treatment of chronic heart failure and their effects on mortality in this patient population. In comparison to captopril, losartan has been shown to have similar benefits in cardiovascular mortality and morbidity. In patients with systolic dysfunction who are intolerant to ACE-Is, candesartan has been shown to reduce cardiovascular mortality and hospital admissions for heart failure. In combination with ACE-Is, candesartan and valsartan have been shown to improve heart failure morbidity and, with candesartan, reduced cardiovascular mortality in those with systolic dysfunction. These 2 trials show conflicting mortality information regarding the use of triple therapy with ACE-Is, ARBs, and beta-blockers for systolic dysfunction. In patients with heart failure but preserved systolic dysfunction, candesartan showed no effects on mortality and only modest effects on morbidity.
cozaar starting dose
To determine whether high protein feeding throughout development affects renal growth, renal hemodynamics, and the intrarenal distribution of renin and its mRNA in the adult animal, male Wistar rats were fed diets containing either 20% protein [normal (NP), n = 12] or 40% protein [high (HP), n = 12] from weaning until studied at 6 or 12 wk of age. Kidney weight, kidney weight-to-body weight ratio, cortical DNA content, and cortical protein-to-DNA ratio were higher in HP- than in NP-fed rats at 6 and 12 wk of age. Somatic and kidney growth response to HP was blunted by angiotensin II type 1 receptor antagonist Dup 753. Glomerular filtration rate and renal plasma flow were higher in HP- than in NP-fed rats at 6 and 12 wk of age. The intrarenal distribution of renin and renin mRNA, assessed by immunocytochemistry and in situ hybridization, respectively, were markedly different between the two groups. In NP-fed rats, renin and renin mRNA were confined to a juxtaglomerular location. In HP-fed rats, renin and its mRNA extended proximally along the afferent arterioles. The percentage of visible afferent arteriolar length containing renin or renin mRNA was higher in HP-fed rats (60 +/- 3.2 and 61 +/- 3.9%, respectively) than in NP-fed rats (39 +/- 2.5 and 33 +/- 0.6%; P less than 0.05). Also, the percentage of juxtaglomerular apparatuses (JGAs) containing renin or renin mRNA was higher in HP-fed rats (80 +/- 1.6 and 72 +/- 2%, respectively), than in NP-fed rats (46 +/- 2.2 and 40 +/- 4%; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
cozaar medication classification
Activation of the renin-angiotensin system both systemically and locally seems to be of importance for cardiovascular hypertrophy and remodelling. The octapeptide angiotensin II definitively plays a central role. In the reversal, for example, of left ventricular hypertrophy, so far the most important independent risk factor for an adverse outcome, blocking of the renin-angiotensin system with ACE inhibition has been shown to be particularly effective. In cardiac tissue, however, ACE inhibition has been suggested to inhibit only a fraction of angiotensin II formed, indicating that other enzymatic pathways can be of importance. From a theoretical point of view a more complete blockade of the angiotensin II type 1 receptor would offer a more effective attenuation of the unfavourable effect of angiotensin II. Experimentally, losartan, a novel selective angiotensin II receptor type 1 antagonist has been shown to decrease cardiac hypertrophic response in models of both hypertension and volume cardiac hypertrophy as well as reverse hypertrophy in spontaneously hypertensive rats. TCV-116, another selective angiotensin II antagonist, also effectively reverses cardiac hypertophy and interstitial fibrosis in the rat. The only report so far regarding the effect of angiotensin II blockade on cardiac hypertrophy in essential hypertension suggests a more favourable short-term effect on cardiac hypertrophy for the same blood pressure reduction with losartan compared with atenolol in a small population of mild to moderate hypertensives. In the perspective of the well-established positive effects of ACE inhibition on the remodelling process in the remaining viable myocardium after myocardial infarction, involving myocyte hypertrophy, interstitial fibrosis and progressive dilatation, it is reassuring that angiotensin II blockade has been shown to perform equally well as ACE inhibition after experimental coronary ligation. In summary, the development of cardiovascular hypertrophy in hypertension is a serious prognostic indicator and selective angiotensin II blockade is a new anti-hypertensive treatment modality with promising properties, especially for prevention and reversal of cardiac hypertrophy including pathological fibrosis and cardiac remodelling after myocardial infarction. Thus, taking into account the shortcomings of today's anti-hypertensive treatment to achieve normalisation of excessive cardiovascular morbidity and mortality, as well as the seemingly great importance of the renin-angiotensin system for hypertension-induced functional and structural abnormalities, a therapy based on a specific All antagonist could offer obvious advantages in a high risk hypertensive patient with cardiovascular hypertrophy. This hypothesis will be investigated in a large prospective trial (Losartan Intervention For End-point reduction in hypertension: The LIFE Study).