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https://www.readbyqxmd.com/read/28548953/from-rapalogs-to-anti-aging-formula
#1
Mikhail V Blagosklonny
Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545667/arctigenin-suppresses-renal-interstitial-fibrosis-in-a-rat-model-of-obstructive-nephropathy
#2
Ao Li, Xiaoxun Zhang, Mao Shu, Mingjun Wu, Jun Wang, Jingyao Zhang, Rui Wang, Peng Li, Yitao Wang
BACKGROUND: Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. PURPOSE: The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28544543/acute-toll-like-receptor-4-activation-impairs-rat-renal-microvascular-autoregulatory-behaviour
#3
Justin P Van Beusecum, Shali Zhang, Anthony K Cook, Edward W Inscho
AIM: Little is known about how toll-like receptor 4 (TLR4) influences the renal microvasculature. We hypothesized that acute TLR4 stimulation with lipopolysaccharide (LPS) impairs afferent arteriole autoregulatory behaviour, partially through reactive oxygen species (ROS). METHODS: We assessed afferent arteriole autoregulatory behaviour after LPS treatment (1 mg kg(-1) ; i.p.) using the in vitro blood perfused juxtamedullary nephron preparation. Autoregulatory behaviour was assessed by measuring diameter responses to step-wise changes in renal perfusion pressure...
May 25, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28542215/treatment-with-enalapril-and-not-diltiazem-ameliorated-progression-of-chronic-kidney-disease-in-rats-and-normalized-renal-at1-receptor-expression-as-measured-with-pet-imaging
#4
Basma Ismail, Rob A deKemp, Etienne Croteau, Tayebeh Hadizad, Kevin D Burns, Rob S Beanlands, Jean N DaSilva
ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8-10 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28541956/nitric-oxide-pathway-presumably-does-not-contribute-to-antianxiety-and-memory-retrieval-effects-of-losartan
#5
Iraj Aghaei, Shokouh Arjmand, Shahrokh Yousefzadeh Chabok, Mahdi Tondar, Mohammad Shabani
Nitric oxide (NO) and angiotensin (AT) receptors have demonstrated well-established interactions in various physiological phenomena. AT1 receptors can play a part in stress-induced activation of the hypothalamic-pituitary-adrenal axis; also, angiotensinergic neurotransmission plays a pivotal role in stress-evoked physiological responses. On the basis of the stress-modulating characteristics of NO, AT1, and AT2 receptors, the present study evaluated the roles of NO and AT1 receptors in the attenuation of stress-induced anxiety-like behaviors after administration of losartan, an AT1 antagonist...
May 24, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28540409/angiotensin-ii-induces-calcium-calcineurin-signaling-and-podocyte-injury-by-downregulating-microrna-30-family-members
#6
Yue Zhao, Junnan Wu, Mingchao Zhang, Minlin Zhou, Feng Xu, Xiaodong Zhu, Xianguang Zhou, Yue Lang, Fan Yang, Shifeng Yun, Shaolin Shi, Zhihong Liu
Angiotensin II (AngII) is capable of inducing calcium/calcineurin signaling and podocyte injury; however, the precise underlying mechanism is not well understood. Because we have previously demonstrated that microRNA-30s (miR-30s) inhibit calcium/calcineurin signaling in podocytes, we hypothesize that AngII may induce podocyte injury by downregulating miR-30s and thereby activating calcium/calcineurin signaling. To test this hypothesis, we used an AngII-induced podocyte injury mouse model. The mice were treated with AngII via infusion for 28 days, which resulted in hypertension, albuminuria, and glomerular damage...
May 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28535536/losartan-preserves-erectile-function-by-suppression-of-apoptosis-and-fibrosis-of-corpus-cavernosum-and-corporal-veno-occlusive-dysfunction-in-diabetic-rats
#7
Wen Ji Li, Mingxi Xu, Meng Gu, Da-Chao Zheng, Jianhua Guo, Zhikang Cai, Zhong Wang
BACKGROUND/AIMS: Transforming growth factor-β1 (TGF-β1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. METHODS: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28529582/angiotensin-ii-receptor-blockers-induce-autophagy-in-prostate-cancer-cells
#8
Yunseo Woo, Yu-Jin Jung
Angiotensin II receptor blockers (ARBs) are anti-hypertensive drugs that competitively inhibit the binding of angiotensin II to its receptor, resulting in blood vessel dilation and the reduction of blood pressure. These antagonists are also known as sartans, and are a group of pharmaceuticals that possess tetrazole or imidazole groups. In the present study, the anticancer and antimetastatic effects of the ARBs fimasartan, losartan, eprosartan and valsartan on the human prostate cancer PC-3, DU-145 and LNCap-LN3 cell lines were investigated in vitro...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28523858/clinical-signs-diagnostics-and-successful-treatment-of-a-myocarditis-in-an-adult-chimpanzee-pan-troglodytes
#9
Martine van Zijll Langhout, Marno Wolters, Katalin M Horvath, Harold Thiesbrummel, Paul Smits, Hester van Bolhuis, Victor van der Hulst, Robert Riezebos
A chimpanzee (Pan troglodytes) was presented with lethargic behaviour. Echocardiography and abnormal cardiac and inflammatory biomarkers revealed a myocarditis. The animal fully recovered after prolonged treatment with losartan and carvedilol. This is the first report of the diagnosis and successful treatment of myocarditis in this species.
May 19, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28521173/thymoquinone-ameliorates-renal-damage-in-unilateral-ureteral-obstruction-in-rats
#10
Sara Hosseinian, Abolfazl Khajavi Rad, Alireza Ebrahimzadeh Bideskan, Mohammad Soukhtanloo, Hamidreza Sadeghnia, Mohammad Naser Shafei, Fatemeh Motejadded, Reza Mohebbati, Samira Shahraki, Farimah Beheshti
BACKGROUND: It is well established that renin-angiotensin system (RAS) play a central role in pathophysiology of renal damage following unilateral ureteral obstruction (UUO). The present study investigated the effects of thymoquinone and RAS blockade on renal tissue damage and renal expression of angiotensin II after UUO in rats. METHODS: Forty male rats were divided to five groups: Sham-operated group, UUO group and rats with UUO treated with losartan, captopril and thymoquinone...
March 14, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28518223/low-shear-stress-induces-endothelial-reactive-oxygen-species-via-the-at1r-enos-no-pathway
#11
Yuelin Chao, Peng Ye, Linlin Zhu, Xiangquan Kong, Xinliang Qu, Junxia Zhang, Jie Luo, Hongfeng Yang, Shaoliang Chen
Reactive oxygen species (ROS) contribute to many aspects of physiological and pathological cardiovascular processes. However, the underlying mechanism of ROS induction by low shear stress (LSS) remains unclear. Accumulating evidence has shown that the angiotensin II type 1 receptor (AT1R) is involved in inflammation, apoptosis, and ROS production. Our aim was to explore the role of AT1R in LSS-mediated ROS induction. We exposed human umbilical vein endothelial cells (HUVECs) to LSS (3 dyne/cm(2) ) for different periods of time...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28508969/five-year-follow-up-of-a-case-of-lipoprotein-glomerulopathy-with-apoe-kyoto-mutation
#12
Ryosuke Usui, Masaki Takahashi, Kosaku Nitta, Minako Koike
We report the case of a 34-year-old Japanese male with lipoprotein glomerulopathy (LPG). Renal biopsy showed LPG, and followed by a genetic analysis revealed a mutation in apolipoprotein E gene (APOE Kyoto; Arg25Cys). We started treatment with probucol, bezafibrate, losartan, and allopurinol. Urinary protein decreased in response to treatment but has remained at about 1.27 ± 0.71 g/gCr, and a repeat biopsy which was performed 1 year after the first biopsy showed no clear evidence of pathological remission and complication of other glomerular disease...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28500295/angiotensin-ii-type-1-adenosine-a-2a-receptor-oligomers-a-novel-target-for-tardive-dyskinesia
#13
Paulo A de Oliveira, James A R Dalton, Marc López-Cano, Adrià Ricarte, Xavier Morató, Filipe C Matheus, Andréia S Cunha, Christa E Müller, Reinaldo N Takahashi, Víctor Fernández-Dueñas, Jesús Giraldo, Rui D Prediger, Francisco Ciruela
Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor heteromers. Here, we examined whether A2AR and AT1R may oligomerize in the striatum to synergistically modulate dopaminergic transmission. First, by using bioluminescence resonance energy transfer, we demonstrated a physical AT1R-A2AR interaction in cultured cells...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28499935/sub-chronic-lead-exposure-produces-%C3%AE-1-adrenoceptor-downregulation-decreasing-arterial-pressure-reactivity-in-rats
#14
Cindy Medici Toscano, Maylla Ronacher Simões, Maria Jesus Alonso, Mercedes Salaices, Dalton Valentim Vassallo, Mirian Fioresi
Lead is considered a causative factor for hypertension and other cardiovascular diseases. AIMS: To investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β1-adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo. MAIN METHODS: Male Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days...
May 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/28490531/the-effects-of-angiotensin-1-7-on-the-nhe3-exchanger-and-on-ca2-i-in-the-proximal-tubules-of-spontaneously-hypertensive-rats
#15
Regiane Castelo-Branco, Deise Carla Almeida Leite-Dellova, Fernanda Fernandes, Gerhard Malnic, Margarida de Mello-Aires
The acute effects of Ang-(1-7) on the reabsorptive bicarbonate flow (JHCO3-) were evaluated using stationary microperfusion in vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive to H+. In WKY rats, the control JHCO3- was 2.40 ± 0.10 nmol.cm-2.s-1 (28); Losartan (10-7 M) or A779 (10-6 M, a specific Mas antagonist), alone or in combination with Losartan, decreased the JHCO3-. Ang-(1-7) had biphasic effects on JHCO3-: at 10-9 M, it inhibited and at 10-6, it stimulated the flow...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28483563/losartan-a-selective-antagonist-of-at1-receptor-attenuates-seawater-inhalation-induced-lung-injury-via-modulating-jak2-stats-and-apoptosis-in-rat
#16
Congcong Li, Liyan Bo, Pengcheng Li, Xi Lu, Wangping Li, Lei Pan, Yani Sun, Deguang Mu, Wei Liu, Faguang Jin
Losartan is a selective antagonist of AngⅠ type (AT1) receptor of Angiotensin Ⅱ (Ang Ⅱ), which is widely used as a clinical medicine for the hypertension. Recent studies have shown that losartan was shown to protect from acute lung injury (ALI). However, the underlying mechanism remains unclear. The aim of this research was to clarify whether Ang Ⅱ participated in the inflammatory response of ALI induced by seawater inhalation, and whether losartan had the protective effects on ALI by blocking the combination of Ang Ⅱ and AT1 receptor...
May 5, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28481921/low-sodium-diet-induces-atherogenesis-regardless-of-lowering-blood-pressure-in-hypertensive-hyperlipidemic-mice
#17
Fernanda B Fusco, Diego J Gomes, Kely C S Bispo, Veronica P Toledo, Denise F Barbeiro, Vera L Capelozzi, Luzia N S Furukawa, Ana P P Velosa, Walcy R Teodoro, Joel C Heimann, Eder C R Quintao, Marisa Passarelli, Edna R Nakandakare, Sergio Catanozi
This study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids...
2017: PloS One
https://www.readbyqxmd.com/read/28479361/impact-of-fda-approved-drugs-on-the-prostaglandin-transporter-oatp2a1-slco2a1
#18
Shunsuke Kamo, Takeo Nakanishi, Rika Aotani, Yoshinobu Nakamura, Tomoka Gose, Ikumi Tamai
To understand interaction of drugs with the prostaglandin transporter OATP2A1/SLCO2A1 that regulates disposition of prostaglandins, we explored impacts of 636 drugs in an FDA-approved drug library on 6-carboxyfluorescein (6-CF) uptake by OATP2A1-expressing HEK293 cells (HEK/2A1). Fifty one and 10 drugs were found to inhibit and enhance 6-CF uptake by more than 50%, respectively. Effect of the 51 drugs on 6-CF uptake was positively correlated with PGE2 uptake (r = 0.64, p < 0.001). Among those, 5 drugs not structurally related with prostaglandins, suramin, pranlukast, zafirlukast, olmesartan medoxomil and losartan potassium, exhibited more than 90% PGE2 uptake inhibition...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28476949/angiotensin-iv-receptors-mediate-the-cognitive-and-cerebrovascular-benefits-of-losartan-in-a-mouse-model-of-alzheimer-s-disease
#19
Jessika Royea, Luqing Zhang, Xin-Kang Tong, Edith Hamel
The use of angiotensin receptor blockers (ARBs) correlates with reduced onset and progression of Alzheimer's disease (AD). The mechanism depicting how ARBs, such as losartan, restore cerebrovascular and cognitive deficits in AD is unknown. Here, we propose a mechanism underlying losartan's benefits by selectively blocking the effects of Angiotensin IV (AngIV) at its receptor (AT4R) with divalinal in mice overexpressing the AD-related Swedish and Indiana mutations of the human amyloid precursor protein (APP mice) and wild-type mice...
May 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28475214/the-angiotensin-ii-receptor-type-1b-is-the-primary-sensor-of-intraluminal-pressure-in-cerebral-artery-smooth-muscle-cells
#20
Paulo W Pires, Eun-A Ko, Harry A T Pritchard, Michael Rudokas, Evan Yamasaki, Scott Earley
Myogenic vasoconstriction, which reflects the intrinsic ability of smooth muscle cells to contract in response to increases in intraluminal pressure, is critically important for the autoregulation of blood flow. In SMC from cerebral arteries, increasing intraluminal pressure engages a signalling cascade that stimulates cation influx through transient receptor potential (TRP) melastatin 4 (TRPM4) channels to cause membrane depolarization and vasoconstriction. Substantial evidence indicates that the angiotensin II receptor type 1 (AT1 R) is inherently mechanosensitive and initiates this signalling pathway...
May 5, 2017: Journal of Physiology
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