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Testing the Translational Power of the Zebrafish: An Interspecies Analysis of Responses to Cardiovascular Drugs
The zebrafish is rapidly emerging as a promising alternative in vivo model for the detection of drug-induced cardiovascular effects. Despite its increasing popularity, the ability of this model to inform the drug development process is often limited by the uncertainties around the quantitative relevance of zebrafish responses compared with non-clinical mammalian species and ultimately humans. Here we provide a comparative quantitative analysis of the in vivo cardiovascular responses of zebrafish, rat, dog, and human to three model compounds (propranolol, losartan, and captopril), which act as modulators of two key systems ...
Source: Frontiers in Pharmacology - August 15, 2019 Category: Drugs & Pharmacology Source Type: research

Impact of early life AT1 blockade on adult cardiac morpho-functional changes and the renin-angiotensin system in a model of neonatal high oxygen-induced cardiomyopathy.
Abstract We previously reported that neonatal blockade of angiotensin II AT1 receptor prevents cardiac changes in 4 weeks rats with neonatal hyperoxia-induced cardiomyopathy, a recognized model of prematurity-related deleterious conditions. Considering the importance of AT1 receptor and the renin angiotensin system (RAS) in normal development, the present study aimed to investigate the adult effects of neonatal AT1 blockade on left ventricle (LV) in rats exposed to neonatal hyperoxia. Sprague-Dawley pups were exposed to 80% O2 or room air from days 3-10. AT1 blocker (losartan) or H2O were given by gavage from day ...
Source: European Journal of Pharmacology - July 30, 2019 Category: Drugs & Pharmacology Authors: Bonetto JHP, Fernandes RO, Dartora DR, Flahault A, Sonea A, He Y, Cloutier A, Belló-Klein A, Nuyt AM Tags: Eur J Pharmacol Source Type: research

The holy grail of epilepsy prevention: preclinical approaches to antiepileptogenic treatments.
Abstract A variety of acute brain insults can induce epileptogenesis, a complex process that results in acquired epilepsy. Despite advances in understanding mechanisms of epileptogenesis, there is currently no approved treatment that prevents the development or progression of epilepsy in patients at risk. The current concept of epileptogenesis assumes a window of opportunity following acute brain insults that allows intervention with preventive treatment. Recent results suggest that injury-induced epileptogenesis can be a much more rapid process than previously thought, suggesting that the 'therapeutic window' may...
Source: Neuropharmacology - April 9, 2019 Category: Drugs & Pharmacology Authors: Löscher W Tags: Neuropharmacology Source Type: research

Post-stroke losartan and captopril treatments arrest hemorrhagic expansion in SHRsp without lowering blood pressure.
Abstract We assessed the ability of poststroke losartan and captopril treatment to attenuate hematoma expansion and plasma extravasation after intracerebral hemorrhagic stroke in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp). Cerebrum volume, herniation and surface areas exhibiting new and old hemorrhages and albumin extravasation were measured prior to and after stroke and following 30 and 60 days of post-stroke losartan or captopril treatment in Evans Blue dye perfused brains. Lesion morphology was studied in serial sections. Losartan or captopril treatment initiated at stroke prevented death for 60 da...
Source: Vascular Pharmacology - August 13, 2018 Category: Drugs & Pharmacology Authors: Smeda JS, Watson D, Stuckless J, Neghandi A Tags: Vascul Pharmacol Source Type: research

Cerebrovascular recovery after stroke with individual and combined losartan and captopril treatment of SHRsp.
Abstract We assessed whether the superior restoration of cerebrovascular function after hemorrhagic stroke by losartan versus captopril treatment was due to better BP, uremia, uricaemia, or aldosterone control in Kyoto Wistar stroke-prone-hypertensive rats and evaluated whether elevated angiotensin II (A2) levels enhanced the effectiveness of losartan treatment. Constriction was studied in the middle cerebral arteries (MCAs) using a pressure myograph. Post-stroke survival increased from 21 to 310 and 189days respectively with losartan and captopril treatment. Neither treatment reduced BP, both reversed uremia and ...
Source: Vascular Pharmacology - August 18, 2017 Category: Drugs & Pharmacology Authors: Smeda JS, Daneshtalab N Tags: Vascul Pharmacol Source Type: research

Fimasartan: A New Angiotensin Receptor Blocker
Abstract Fimasartan is the ninth, and most recent, angiotensin II receptor antagonist approved as an antihypertensive agent. Fimasartan, a pyrimidin-4(3H)-one derivative of losartan with the imidazole ring replaced, which enables higher potency and longer duration than losartan. Fecal elimination and biliary excretion are the predominant elimination pathways of fimasartan and the urinary excretion was found to be less than 3 % 24 h after administration. Fimasartan is primarily catabolized by cytochrome P450 isoform 3A and no significant drug interaction was observed when used in combination with hydrochlorothia...
Source: Drugs - June 6, 2016 Category: Drugs & Pharmacology Source Type: research

Effects of salvianolic acid B and tanshinone IIA on the pharmacokinetics of losartan in rats by regulating the activities and expression of CYP3A4 and CYP2C9
Publication date: 2 March 2016 Source:Journal of Ethnopharmacology, Volume 180 Author(s): Rong Wang, Hai Zhang, Yujie Wang, Xiaoyan Yu, Yongfang Yuan Losartan (LST) is a common chemical drug used to treat high blood pressure and reduce the risk of stroke in certain people with heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations containing Danshen indexed in the 2010 Chinese Pharmacopoeia, which are often combined with LST to treat car...
Source: Journal of Ethnopharmacology - February 6, 2016 Category: Drugs & Pharmacology Source Type: research

Perindopril increases the swallowing reflex by inhibiting substance P degradation and tyrosine hydroxylase activation in a rat model of dysphagia.
Abstract Patients with hypertension have a high risk of ischemic stroke and subsequent stroke-associated pneumonia. Stroke-associated pneumonia is most likely to develop in patients with dysphagia. The present study was designed to compare the ameliorative effects of different treatments in rat model of dysphagia. Spontaneously hypertensive rats were treated with bilateral common carotid artery occlusion (BCAO) to induce chronic cerebral hypoperfusion causing disorders of the swallowing reflex. Angiotensin-converting enzyme (ACE) inhibitors (perindopril, imidapril and enalapril), an angiotensin II type 1-receptor ...
Source: European Journal of Pharmacology - November 12, 2014 Category: Drugs & Pharmacology Authors: Ikeda JI, Kojima N, Saeki K, Ishihara M, Takayama M Tags: Eur J Pharmacol Source Type: research

Comparison of the Effects of Amlodipine and Losartan on Blood Pressure and Diurnal Variation in Hypertensive Stroke Patients: A Prospective, Randomized, Double-Blind, Comparative Parallel Study.
CONCLUSIONS: The noninferiority of amlodipine was not confirmed by the per-protocol analysis. However, amlodipine showed a favorable effect on the morning surge. ClinicalTrials.gov identifier: NCT01830517. PMID: 24296324 [PubMed - as supplied by publisher]
Source: Clinical Therapeutics - November 29, 2013 Category: Drugs & Pharmacology Authors: Kwon HM, Shin JW, Lim JS, Hong YH, Lee YS, Nam H Tags: Clin Ther Source Type: research

A review of the use of Angiotensin receptor blockers for the prevention of cardiovascular events in patients with essential hypertension without compelling indications.
CONCLUSIONS: Data supporting the use of ARBs for reducing cardiovascular events in patients with essential hypertension without compelling indications are limited and inconclusive. More studies are needed before ARBs can be routinely recommended as first-line therapy for hypertension management in patients without other compelling indications. PMID: 23585649 [PubMed - in process]
Source: The Annals of Pharmacotherapy - May 1, 2013 Category: Drugs & Pharmacology Authors: Zaiken K, Hudd TR, Cheng JW Tags: Ann Pharmacother Source Type: research