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LaDonya Jackson, Wael Eldahshan, Susan C Fagan, Adviye Ergul
For many years, modulators of the renin angiotensin system (RAS) have been trusted by clinicians for the control of essential hypertension. It was recently demonstrated that these modulators have other pleiotropic properties independent of their hypotensive effects, such as enhancement of cognition. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Interestingly, a crosstalk between the RAS and other systems such as cholinergic, dopaminergic and adrenergic systems have been demonstrated...
March 15, 2018: International Journal of Molecular Sciences
Kotaro Nochioka, Yasuhiko Sakata, Hiroaki Shimokawa
Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system play crucial roles in heart failure with reduced ejection fraction (HFrEF). Clinical trials provide strong evidence of prognostic benefits for combination therapy with angiotensin-converting enzyme inhibitor (ACEI) and β-blocker in the treatment of HFrEF. Angiotensin receptor blocker (ARB) is not superior to ACEI in improving mortality and an alternative for patients who are intolerant to ACEI. Prognostic evidence for triple therapy which combined angiotensin receptor blocker (ARB) and ACEI in addition to β-blocker therapy, is still controversial in HFrEF...
March 15, 2018: Advances in Experimental Medicine and Biology
Fernando Pedro de Souza-Neto, Melissa Carvalho Santuchi, Mario de Morais E Silva, Maria José Campagnole-Santos, Rafaela Fernandes da Silva
PURPOSE OF REVIEW: The purpose of this review was to summarize the current knowledge on the role of angiotensin-(1-7) [Ang-(1-7)] and alamandine in experimental hypertension and atherosclerosis. RECENT FINDINGS: The renin-angiotensin system (RAS) is a very complex system, composed of a cascade of enzymes, peptides, and receptors, known to be involved in the pathogenesis of hypertension and atherosclerosis. Ang-(1-7), identified and characterized in 1987, and alamandine, discovered 16 years after, are the newest two main effector molecules from the RAS, protecting the vascular system against hypertension and atherosclerosis...
March 14, 2018: Current Hypertension Reports
Pablo Garrido-Gil, Antonio Dominguez-Meijide, Rosario Moratalla, Maria J Guerra, Jose L Labandeira-Garcia
Gastrointestinal dysfunction is a common problem in the elderly. Aging-related changes in interactions between local dopaminergic and renin-angiotensin systems (RAS) have been observed in the brain, renal and vascular tissues. However, it is not known if these interactions also occur in the gut, and are dysregulated with aging. We showed a mutual regulation between the colonic dopaminergic system and RAS using young and aged mice deficient for major angiotensin and dopamine receptors. Aged rats showed a marked decrease in colonic dopamine D2 receptor expression, together with an increase in angiotensin type 1 (AT1) receptor expression, a decrease in angiotensin type 2 (AT2) receptor expression (i...
February 16, 2018: Oncotarget
Hong-Ren Yu, You-Lin Tain, Mao-Meng Tiao, Chih-Cheng Chen, Jiunn-Ming Sheen, I-Chun Lin, Shih-Wen Li, Ching-Chou Tsai, Yu-Ju Lin, Kai-Sheng Hsieh, Li-Tung Huang
BACKGROUND: Hypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero. Recent studies demonstrated the potent contribution of adipose tissue's renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP). In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue. METHODS: RAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined...
March 14, 2018: Lipids in Health and Disease
Eva Nüsken, Jörg Dötsch, Lutz T Weber, Kai-Dietrich Nüsken
Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life...
2018: Frontiers in Pediatrics
Natalia P Rocha, Fernando M Bastos, Érica L M Vieira, Thiago R R Prestes, Katia D da Silveira, Mauro M Teixeira, Ana Cristina Simões E Silva
OBJECTIVE: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules...
March 10, 2018: Jornal de Pediatria
Shin Ishikane, Fumi Takahashi-Yanaga
Hypertension, which often exists as a comorbid condition in cancer patients, is considered as a factor affecting cancer progression. The renin-angiotensin system (RAS) plays an important role in theregulation of blood pressure, and angiotensin II (Ang II) is a well-known pressor peptide in RAS. There is also accumulated evidence indicating that Ang II plays a critical role in the metastasis of various cancers by modulating adhesion, migration invasion, proliferation, and angiogenesis. Consistent with this, large epidemiological studies have reported the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors and Ang II type 1 receptor blockers (ARBs) against cancer metastasis; however, some of the results remain controversial...
March 10, 2018: Biochemical Pharmacology
Martina Tetti, Silvia Monticone, Jacopo Burrello, Patrizia Matarazzo, Franco Veglio, Barbara Pasini, Xavier Jeunemaitre, Paolo Mulatero
Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in germline mutations of the SCNN1A , SCNN1B and SCNN1G genes, encoding the α, β, and γ-subunits of the epithelial Na⁺ channel (ENaC), respectively. To date, 31 different causative mutations have been reported in 72 families from four continents. The majority of the substitutions cause an increased expression of the channel at the distal nephron apical membrane, with subsequent enhanced renal sodium reabsorption...
March 11, 2018: International Journal of Molecular Sciences
Junya Hashimoto, Yuko Hamasaki, Yusuke Takahashi, Mai Kubota, Taketo Yanagisawa, Yoshihiro Itabashi, Masaki Muramatsu, Takeshi Kawamura, Naonori Kumagai, Yoko Ohwada, Ken Sakai, Seiichiro Shishido
AIM: Epstein syndrome is a hereditary disease characterised by macrothrombocytopaenia and progressive nephritis. The abnormality of the MYH9 gene has a strong relationship to the severity of the disease. Severe Epstein syndrome progresses to end-stage renal disease rapidly after adolescence. There is no established therapy. We sought to clarify appropriate management of Epstein syndrome nephropathy. METHODS: Epstein syndrome patients who underwent renal transplantation at our institution between March 2009 and March 2017 were enrolled...
March 13, 2018: Nephrology
Maryam Maleki, Jalal Hasanshahi, Fatemeh Moslemi
Background: Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Materials and Methods: Sixty-three Wistar male and female rats were used...
2018: Advanced Biomedical Research
Kevin Kuriakose, Whitney Jones-Nesbitt, Matthew Greene, Bryan Harris
A woman in her late 60s with disseminated histoplasmosis was treated with posaconazole since first-line therapies were not tolerated. She subsequently presented with decompensated heart failure, hypertension, and hypokalemia. Labs revealed low renin and aldosterone levels. A potential mechanism is inhibition of the enzyme 11 beta-hydroxysteroid dehydrogenase 2, with resultant apparent mineralocorticoid excess.
March 12, 2018: Antimicrobial Agents and Chemotherapy
Věra Čertíková Chábová, Petr Kujal, Petra Škaroupková, Zdeňka Varňourková, Šárka Vacková, Zuzana Husková, Soňa Kikerlová, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Iwona Baranowska, Sung Hee Hwang, Bruce D Hammock, John D Imig, Vladimír Tesař, Ludek Červenka
BACKGROUND/AIMS: We found recently that increasing renal epoxyeicosatrienoic acids (EETs) levels by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, shows renoprotective actions and retards the progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). This prompted us to examine if additional protection is provided when sEH inhibitor is added to the standard renin-angiotensin system (RAS) blockade, specifically in rats with established CKD...
March 6, 2018: Kidney & Blood Pressure Research
Ma'mon M Hatmal, Mutasem O Taha
We previously combined molecular dynamics (classical or simulated annealing) with ligand-receptor contacts analysis as means to extract valid pharmacophore model(s) from single ligand-receptor complexes. However, molecular dynamics methods are computa-tionally expensive and time consuming. Here we describe a novel method for extracting valid pharmacophore model(s) from a single crystallographic structure within reasonable time scale. The new method is based on ligand-receptor contacts analysis following en-ergy relaxation of predetermined set of randomly deformed complexes generated from the targeted crystallographic structure...
March 12, 2018: Journal of Chemical Information and Modeling
Wessel M C M Vorselaars, Gerlof D Valk, Menno R Vriens, Jan Westerink, Wilko Spiering
OBJECTIVE: The aldosterone-to-renin ratio is widely used and is the recommended screening modality for primary aldosteronism by the Endocrine Society Guideline. However, studies on its diagnostic accuracy have been inconsistent, which is mainly because of methodological limitations. We set out to evaluate this diagnostic value by using a highly standardized study protocol, which is in line with the Endocrine Society Guideline recommendations regarding indications for screening, testing conditions and reference standards in daily clinical practice...
March 9, 2018: Journal of Hypertension
P Kala, L Sedláková, P Škaroupková, L Kopkan, Z Vaňourková, M Táborský, A Nishiyama, S H Hwang, B D Hammock, J Sadowski, V Melenovský, J D Imig, L Červenka
We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR...
March 12, 2018: Physiological Research
Takashi Komatsu, Fusanori Kunugita, Mahito Ozawa, Yoshihiro Satoh, Reisuke Yoshizawa, Shingen Owada, Youhei Sawa, Yoshihiro Morino, Motoyuki Nakamura
Background and methods There is little information concerning the influence of the heart rhythm on the vascular endothelial function in patients with non-valvular atrial fibrillation (AF) compared with studies concerning sinus rhythm (SR). The present study included paroxysmal (n=184) or chronic (n=53) AF patients without heart failure and control subjects with SR (n=79) matched for age, gender and the CHA2 DS2 -VASc score. Paroxysmal AF was defined as episodes that terminated spontaneously within 7 days, while chronic AF was defined as longstanding AF that was refractory to cardioversion for 12 months or longer...
March 9, 2018: Internal Medicine
Karin Rådholm, Gemma Figtree, Vlado Perkovic, Scott D Solomon, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Terrance D Barrett, Wayne Shaw, Mehul Desai, David R Matthews, Bruce Neal
BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure and cardiovascular death overall, in those with and without a baseline history of heart failure, and in other participant subgroups. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks...
March 11, 2018: Circulation
Hamish C G Prosser, Omar Azzam, Markus P Schlaich
Resistant hypertension is commonly defined as office blood pressure above recommended target despite the use of optimal doses of at least three antihypertensive drugs including a diuretic. Australian guidelines recommend combination of blockers of the renin-angiotensin system, either ACE inhibitors or angiotensin receptor blockers, with calcium channel blockers and diuretics as the preferred triple therapy. A substantial proportion of hypertensive patients will require additional pharmacotherapy to achieve or get close to target blood pressure levels...
March 1, 2018: Heart, Lung & Circulation
Brenda de Oliveira da Silva, Luciane Carla Alberici, Letícia Ferreira Ramos, Caio Mateus Silva, Marina Bonfogo da Silveira, Carlos R P Dechant, Scott L Friedman, Kumiko Koibuchi Sakane, Letícia Rocha Gonçalves, Karen C M Moraes
The development of new therapeutic strategies to control or reverse hepatic fibrosis requires thorough knowledge about its molecular and cellular basis. It is known that the heptapeptide angiotensin-(1-7) [ang-(1-7)] can reduce hepatic fibrosis and steatosis in vivo; therefore, it is important to uncover the mechanisms regulating its activity and cellular model of investigation. Ang-(1-7) is a peptide of the renin-angiotensin system (RAS), and here we investigated its modulatory effect on the expression pattern of microRNAs (miRNAs) in hepatic stellate cells (HSCs) LX-2, which transdifferentiate into fibrogenic and proliferative cells...
March 7, 2018: International Journal of Biochemistry & Cell Biology
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