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losartan restores

Anthony Accorsi, Ajay Kumar, Younghwa Rhee, Alex Miller, Mahasweta Girgenrath
As the complexities of dystrophic pathology have been elucidated over the last few years, it has become increasingly clear that primary monogenetic defects result in multiple secondary pathologies capable of autonomously driving disease progression. Consequently, single-mode therapies fail to comprehensively ameliorate all aspects of pathology. Lama2-related muscular dystrophy (MDC1A) is a devastating congenital muscular dystrophy caused by mutations in the LAMA2 gene that results in multi-faceted secondary pathologies that include inflammation, fibrosis, apoptosis, and necrosis leading to severe muscle weakness and minimal postnatal growth...
October 24, 2016: Human Molecular Genetics
Gustavo Costa, Manel Garabito, Francesc Jiménez-Altayó, Yara Onetti, Manel Sabate, Elisabet Vila, Ana Paula Dantas
Aging is a cardiovascular risk factor partially related to activation of the Renin-Angiotensin System (RAS). RAS activation is also influenced by sex. In this regard, our study aims to determine whether sex-associated differences in RAS contribute to a differential regulation of vascular aging and associated dysfunction. Male and female outbreed CD-1 mice were studied at 3 and 12months of age (M). Contribution of RAS was determined by treating mice from 3M to 12M with the AngII type 1 receptor blocker losartan (0...
October 3, 2016: Experimental Gerontology
Danijela Karanovic, Jelica Grujic-Milanovic, Zoran Miloradovic, Milan Ivanov, Djurdjica Jovovic, Una-Jovana Vajic, Maja Zivotic, Jasmina Markovic-Lipkovski, Nevena Mihailovic-Stanojevic
Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy...
2016: PloS One
Jamaira A Victorio, Stefano P Clerici, Roberto Palacios, María J Alonso, Dalton V Vassallo, Iris Z Jaffe, Luciana V Rossoni, Ana P Davel
Sustained stimulation of β-adrenoceptors (β-ARs) and activation of renin-angiotensin-aldosterone system are common features of cardiovascular diseases with rising sympathetic activation, including essential hypertension, myocardial infarction, and heart failure. In this study, we investigated the role of AT1 receptor and mineralocorticoid receptor (MR) in the vascular alterations caused by β-AR overstimulation. β-AR overstimulation with associated cardiac hypertrophy and increased vasoconstrictor response to phenylephrine in aorta were modeled in rats by 7-day isoproterenol treatment...
September 2016: Hypertension
Panayiota Papadopoulos, Xin-Kang Tong, Hans Imboden, Edith Hamel
Alterations of the renin-angiotensin system have been implicated in the pathogenesis of Alzheimer's disease. We tested the efficacy of losartan (10 mg/kg/day for three months), a selective angiotensin II type 1 receptor antagonist, in alleviating cerebrovascular and cognitive deficits in double-transgenic mice (six months at endpoint) that overexpress a mutated form of the human amyloid precursor protein (APPSwe,Ind) and a constitutively active form of the transforming growth factor-β1, thereafter named A/T mice...
July 7, 2016: Journal of Cerebral Blood Flow and Metabolism
Jorge Chahla, Robert F LaPrade, Rodrigo Mardones, Johnny Huard, Marc J Philippon, Shane Nho, Omer Mei-Dan, Cecilia Pascual-Garrido
Treatment of hip cartilage disease is challenging, and there is no clear algorithm to address this entity. Biomarkers are arising as promising diagnostic tools because they could play a role in the early assessment of the prearthritic joint and as a prognostic factor before and after treatment. The potential effect of biomarkers may be used to categorize individuals at risk of evolving to severe osteoarthritis, to develop new measures for clinical progression of the disease, and to develop new treatment options for the prevention of osteoarthritis progression...
July 1, 2016: Orthopedics
Tae-Sun Ha, Hye-Young Park, Su-Bin Seong, Hee-Yul Ahn
Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II...
April 2016: Journal of Korean Medical Science
Hanan S Anbar, George S G Shehatou, Ghada M Suddek, Nariman M Gameil
This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks...
June 5, 2016: European Journal of Pharmacology
C Hass, B P Panda, R Khanam, A K Najmi, M Akhtar
BACKGROUND: Myocardial infarction is an alarming health issue, needs great attention. The present study investigated the role of histamine-H3 receptor (H3R) agonist imetit in relationship to sympathetic and renin angiotensin system in Wistar rats. MATERIALS AND METHODS: Subcutaneous injection of isoproterenol (85 mg/kg) on last 2 consecutive days in per se group and 7 days treatment of different groups at 24 h interval induced myocardial infarction in Wistar rats...
June 2016: Drug Research
M Mishima, T Hamada, N Maharani, N Ikeda, T Onohara, T Notsu, H Ninomiya, S Miyazaki, E Mizuta, S Sugihara, M Kato, K Ogino, M Kuwabara, Y Hirota, A Yoshida, N Otani, N Anzai, I Hisatome
BACKGROUND: Although urate impaired the endothelial function, its underlying mechanism remains unknown. We hypothesized that urate impaired nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) via activation of uric acid transporters (UATs). PURPOSE AND METHOD: In the present study, we studied effects of urate on NO production and eNOS protein expression in HUVEC cells in the presence and absence of urate lowering agents using molecular biological and biochemical assays...
May 2016: Drug Research
Paramita Pati, David J R Fulton, Zsolt Bagi, Feng Chen, Yusi Wang, Julia Kitchens, Lisa A Cassis, David W Stepp, R Daniel Rudic
Blood pressure exhibits a robust circadian rhythm in health. In hypertension, sleep apnea, and even shift work, this balanced rhythm is perturbed via elevations in night-time blood pressure, inflicting silent damage to the vasculature and body organs. Herein, we examined the influence of circadian dysfunction during experimental hypertension in mice. Using radiotelemetry to measure ambulatory blood pressure and activity, the effects of angiotensin II administration were studied in wild-type (WT) and period isoform knockout (KO) mice (Per2-KO, Per2, 3-KO, and Per1, 2, 3-KO/Per triple KO [TKO] mice)...
March 2016: Hypertension
Roxana Rodríguez-Romo, Kenia Benítez, Jonatan Barrera-Chimal, Rosalba Pérez-Villalva, Arturo Gómez, Diana Aguilar-León, Jesús F Rangel-Santiago, Sara Huerta, Gerardo Gamba, Norma Uribe, Norma A Bobadilla
Despite clinical recovery of patients from an episode of acute kidney injury (AKI), progression to chronic kidney disease (CKD) is possible on long-term follow-up. However, mechanisms of this are poorly understood. Here, we determine whether activation of angiotensin-II type 1 receptors during AKI triggers maladaptive mechanisms that lead to CKD. Nine months after AKI, male Wistar rats develop CKD characterized by renal dysfunction, proteinuria, renal hypertrophy, glomerulosclerosis, tubular atrophy, and tubulointerstitial fibrosis...
February 2016: Kidney International
Kee-Ho Song, Jung-Hyun Park, Inho Jo, Joong-Yeol Park, Jungwon Seo, Soon Ae Kim, Du-Hyong Cho
Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor α (TNFα), which leads to arteriosclerotic cardiovascular diseases such as myocardial infarction. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), is prescribed for treatment of hypertensive patients with concurrent diabetes mellitus (DM). Although a few clinical trials have suggested that telmisartan decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive...
March 2016: Vascular Pharmacology
Reem Ismael-Badarneh, Julia Guetta, Geula Klorin, Gidon Berger, Niroz Abu-Saleh, Zaid Abassi, Zaher S Azzam
Active alveolar fluid clearance is important in keeping airspaces free of edema. Angiotensin II plays a role in the pathogenesis of hypertension, heart failure and others. However, little is known about its contribution to alveolar fluid clearance. Angiotensin II effects are mediated by two specific receptors; AT1 and AT2. The localization of these two receptors in the lung, specifically in alveolar epithelial cells type II, was recently reported. We hypothesize that Angiotensin II may have a role in the regulation of alveolar fluid clearance...
2015: PloS One
Lin Wu, Pi-Qi Zhou, Ji-Wen Xie, Rui Zhu, Sun-Chang Zhou, Geng Wang, Zhong-Xu Wu, Sha Hao
In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring the self-regulation and balance of the renin-angiotensin system (RAS), 33 specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows: G1, the sham group (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan 0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8)...
August 2015: Journal of Huazhong University of Science and Technology. Medical Sciences
Venkatachalam Gopi, Vimala Subramanian, Senthamizharasi Manivasagam, Elangovan Vellaichamy
Atrial natriuretic peptide (ANP)/natriuretic peptide receptor-A (NPR-A) system is suggested as an endogenous anti-hypertrophic protective mechanism of the heart. We have shown previously that Angiotensin II (ANG II), an effector molecule of renin-angiotensin-aldosterone system, down-regulates NPR-A expression and its activity in vivo rat heart. However, the underlying mechanism by which ANG II down-regulates NPR-A expression in the heart is not well understood. Hence, the present investigation was aimed to determine whether ANG II-stimulated reactive oxygen species (ROS) and NF-κB are involved in the down-regulation of NPR-A activity in H9c2 (2-1) cardiac myoblast cells...
November 2015: Molecular and Cellular Biochemistry
Anil Kumar, Barinder Singh, Jitendriya Mishra, Sangeeta Pilkhwal Sah, Raghavender Pottabathini
Potential role of angiotensin-II and cyclooxygenase have been suggested in the pathophysiology of chronic fatigue stress. The present study has been designed to evaluate the neuroprotective effect of losartan and its interaction with nimesulide against chronic fatigue stress and related complications in mice. In the present study, male Laca mice (20-30 g) were subjected to running wheel activity test session (RWATS) for 6 min daily for 21 days. Losartan, nimesulide and their combinations were administered daily for 21 days, 45 min before being subjected to RWATS...
December 2015: Inflammopharmacology
O Busnadiego, D Gorbenko Del Blanco, J González-Santamaría, J P Habashi, J F Calderon, P Sandoval, D Bedja, J Guinea-Viniegra, M Lopez-Cabrera, T Rosell-Garcia, J M Snabel, R Hanemaaijer, A Forteza, H C Dietz, G Egea, F Rodriguez-Pascual
Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-β (TGF-β)- and angiotensin II-dependent pathways, alterations in the vascular extracellular matrix (ECM) may also play a role in the onset and progression of the aortic disease...
August 2015: Journal of Molecular and Cellular Cardiology
Tiago J Costa, Graziela S Ceravolo, Rosangela A dos Santos, Maria Aparecida de Oliveira, Priscila X Araújo, Luciana R Giaquinto, Rita C Tostes, Eliana H Akamine, Zuleica B Fortes, Ana Paula Dantas, Maria Helena C Carvalho
Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats...
April 1, 2015: American Journal of Physiology. Heart and Circulatory Physiology
Francesca Querques, Bruno Cantilena, Carmine Cozzolino, Maria Teresa Esposito, Fabiana Passaro, Silvia Parisi, Barbara Lombardo, Tommaso Russo, Lucio Pastore
Clinical studies of large human populations and pharmacological interventions in rodent models have recently suggested that anti-hypertensive drugs that target angiotensin II (Ang II) activity may also reduce loss of bone mineral density. Here, we identified in a genetic screening the Ang II type I receptor (AT1R) as a potential determinant of osteogenic differentiation and, implicitly, bone formation. Silencing of AT1R expression by RNA interference severely impaired the maturation of a multipotent mesenchymal cell line (W20-17) along the osteoblastic lineage...
July 2015: Journal of Cellular Physiology
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