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Angiotensin receptor blockers and endothelin

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https://www.readbyqxmd.com/read/28520568/endothelin-a-receptor-antagonists-in-diabetic-kidney-disease
#1
Panagiotis I Georgianos, Rajiv Agarwal
PURPOSE OF REVIEW: Despite optimal therapy of diabetic nephropathy with agents blocking the renin-angiotensin-aldosterone system, the residual risk of nephropathy progression to end-stage renal disease (ESRD) remains high. The purpose of this review is to discuss the potential role of endothelin antagonism as a therapeutic tool to reduce residual proteinuria and delay kidney injury progression among patients with diabetic nephropathy. RECENT FINDINGS: Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert proteinuria lowering and nephroprotective actions in experimental models of diabetic nephropathy...
May 17, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28287881/renin-angiotensin-system-blockade-alone-or-combined-with-eta-receptor-blockade-effects-on-the-course-of-chronic-kidney-disease-in-5-6-nephrectomized-ren-2-transgenic-hypertensive-rats
#2
Lenka Sedláková, Věra Čertíková Chábová, Šárka Doleželová, Petra Škaroupková, Libor Kopkan, Zuzana Husková, Lenka Červenková, Soňa Kikerlová, Ivana Vaněčková, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Petr Kujal, Herbert J Kramer, Luděk Červenka
BACKGROUND: Early addition of endothelin (ET) type A (ETA) receptor blockade to complex renin-angiotensin system (RAS) blockade has previously been shown to provide better renoprotection against progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). In this study, we examined if additional protection is provided when ETA blockade is applied in rats with already developed CKD. METHODS: For complex RAS inhibition, an angiotensin-converting enzyme inhibitor along with angiotensin II type 1 receptor blocker was used...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28060893/positioning-of-tacrolimus-for-the-treatment-of-diabetic-nephropathy-based-on-computational-network-analysis
#3
Constantin Aschauer, Paul Perco, Andreas Heinzel, Judith Sunzenauer, Rainer Oberbauer
OBJECTIVE: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. MATERIALS AND METHODS: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology...
2017: PloS One
https://www.readbyqxmd.com/read/27754186/sp-04-1-the-role-of-natriuretic-peptides-in-the-pathogenesis-of-cardiovascular-diseases
#4
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754015/br-04-1management-of-treatment-resistant-hypertension
#5
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643143/sp-04-1-the-role-of-natriuretic-peptides-in-the-pathogenesis-of-cardiovascular-diseases
#6
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27642926/br-04-1management-of-treatment-resistant-hypertension
#7
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27560156/decreased-risk-of-radiation-pneumonitis-with-coincident-concurrent-use-of-angiotensin-converting-enzyme-inhibitors-in-patients-receiving-lung-stereotactic-body-radiation-therapy
#8
Fiori Alite, Neelam Balasubramanian, William Adams, Murat Surucu, Ibrahim Mescioglu, Matthew M Harkenrider
OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT). METHODS: We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014...
August 24, 2016: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27415977/therapeutic-modulation-of-aortic-stiffness
#9
REVIEW
Ahmed Muzhir Hussein, Ghazwan Shaaya, Rohit Arora, Ali Al-Khazaali, Khalid Al-Khafaji, Hanan K Helu
Aortic stiffness (AS) is an important predictor of cardiovascular morbidity in humans. The present review discusses the possible pathophysiological mechanisms of AS and focuses on a survey of different therapeutic modalities for decreasing AS. The influence of several nonpharmacological interventions is described: decrease body weight, diet, aerobic exercise training, music, and continuous positive airway pressure therapy. The effects of different pharmacological drug classes on AS are also discussed: antihypertensive drugs-renin-angiotensin-aldosterone system drugs, beta-blockers, alpha-blockers, diuretics, and calcium channel blockers (CCBs)-advanced glycation end product cross-link breakers, statins, oral anti-diabetics, anti-inflammatory drugs, vitamin D, antioxidant vitamins, and endothelin-1 receptor antagonists...
November 2016: American Journal of Therapeutics
https://www.readbyqxmd.com/read/27320303/sympathetic-activation-in-heart-failure-a-target-of-therapeutic-approaches
#10
P Schnabel, M Böhm
In heart failure, decreased cardiac output leads to a number of adaptive mechanisms. Among these, neuroendocrine activation including activation of the renin-angiotensin-aldosterone system, augmentation of vasopressin and endothelin release, and activation of the sympathetic nervous system occur. The increase of adrenergic drive is characterized by decreased baroreceptor sensitivity, increased plasma norepinephrine levels and cardiac norepinephrine spillover, and desensitization of postsynaptic β-adrenergic signal transduction...
October 1999: Zeitschrift Für Kardiologie
https://www.readbyqxmd.com/read/27268955/targeting-inflammation-in-diabetic-kidney-disease-early-clinical-trials
#11
REVIEW
Maria Vanessa Perez-Gomez, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Binbin Zheng, Catalina Martín-Cleary, Marta Ruiz-Ortega, Alberto Ortiz, Beatriz Fernandez-Fernandez
INTRODUCTION: The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials. AREAS COVERED: The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action...
September 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27206576/neurohormonal-activation-and-pharmacological-inhibition-in-pulmonary-arterial-hypertension-and-related-right-ventricular-failure
#12
Pietro Ameri, Edoardo Bertero, Giovanni Meliota, Martino Cheli, Marco Canepa, Claudio Brunelli, Manrico Balbi
During the last decade, hyperactivity of the sympathetic nervous and renin-angiotensin-aldosterone systems (SNS and RAAS, respectively) has repeatedly been related to the pathophysiology of pulmonary arterial hypertension (PAH) and PAH-related right ventricular failure (PAH-RVF), raising the question of whether neurohormonal inhibition may be indicated for these conditions. Experimental data indicate that the RAAS may be involved in pulmonary vascular remodeling, which is in fact halted by RAAS antagonism. Favorable actions of β-blockers on the pulmonary vasculature have also been described, even if information about β-adrenergic receptors in PAH is lacking...
September 2016: Heart Failure Reviews
https://www.readbyqxmd.com/read/27129065/raynaud-s-phenomenon-and-digital-ischaemia-pharmacologic-approach-and-alternative-treatment-options
#13
REVIEW
Birgit Linnemann, Matthias Erbe
The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life...
2016: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/27009050/dual-inhibition-of-renin-angiotensin-aldosterone-system-and-endothelin-1-in-treatment-of-chronic-kidney-disease
#14
REVIEW
Radko Komers, Horacio Plotkin
Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients...
May 15, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/26990595/pharmacodynamic-and-pharmacokinetic-profiles-of-sacubitril-valsartan-lcz696-in-patients-with-heart-failure-and-reduced-ejection-fraction
#15
Zhanna Kobalava, Yulia Kotovskaya, Oleg Averkov, Elena Pavlikova, Valentine Moiseev, Diego Albrecht, Priya Chandra, Surya Ayalasomayajula, Margaret F Prescott, Parasar Pal, Thomas H Langenickel, Pierre Jordaan, Iris Rajman
AIMS: Concomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF. METHODS: This was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF ≤ 40%; NYHA class II-IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs])...
August 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/26775568/moderate-additive-effects-of-endothelin-receptor-a-blockade-in-ren-2-transgenic-rats-subjected-to-various-types-of-ras-blockade
#16
Ivana Vaněčková, Lenka Řezáčová, Jaroslav Kuneš, Josef Zicha
AIMS: Chronic endothelin receptor A (ETA) blockade lowered blood pressure (BP) by decreasing angiotensin-dependent vasoconstriction and attenuating calcium influx. We tested whether the addition of ETA blockade to renin-angiotensin system (RAS) blockade would have further effects on the principal vasoactive systems contributing to BP maintenance in Ren-2 transgenic rats (TGR). METHODS: Four-week-old TGR rats were fed with normal-salt diet and given either different renin-angiotensin system (RAS) blockers [angiotensin receptor blocker losartan, angiotensin converting enzyme inhibitor captopril, direct renin inhibitor aliskiren], or ETA blocker (atrasentan) alone, or a combination of atrasentan with RAS blockers for 4weeks...
August 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/26755746/the-emerging-role-of-endothelin-1-in-the-pathogenesis-of-pre-eclampsia
#17
REVIEW
Langeza Saleh, Koen Verdonk, Willy Visser, Anton H van den Meiracker, A H Jan Danser
Pre-eclampsia (PE) is the most frequently encountered medical complication during pregnancy. It is characterized by a rise in systemic vascular resistance with a relatively low cardiac output and hypovolemia, combined with severe proteinuria. Despite the hypovolemia, renin-angiotensin system (RAS) activity is suppressed and aldosterone levels are decreased to the same degree as renin. This suggests that the RAS is not the cause of the hypertension in PE, but rather that its suppression is the consequence of the rise in blood pressure...
October 2016: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/26688921/-first-experience-of-clinical-application-of-lcz696-an-at1-angiotensin-receptors-and-neprilysin-inhibitor-in-patients-with-chronic-heart-failure-and-reduced-ejection-fraction
#18
Zh D Kobalava, E P Pavlikova, O A Averkov, I Merai, L A Babaeva, I M Amirbegishvili, Yu V Kotovskaya, V S Moisfev
UNLABELLED: Simultaneous inhibition of the renin-angiotensin-aldosterone system and the system of degradation of natriuretic peptides can potentially provide unique therapeutic effects in patients with chronic heart failure (CHF) with reduced ejection fraction (EF). Aim of this study was to assess tolerability of therapy with LCZ696--first representative of a class of inhibitors of angiotensin receptor and neutral endopeptidase neprilysin--and to study its pharmacodynamic effects. METHODS: We included into open uncontrolled study 30 patients with stable functional class II-III CHF and EF ≤ 40%...
2015: Kardiologiia
https://www.readbyqxmd.com/read/26631854/renal-denervation-mitigates-cardiac-remodeling-and-renal-damage-in-dahl-rats-a-comparison-with-%C3%AE-receptor-blockade
#19
Heitaro Watanabe, Yoshitaka Iwanaga, Yuki Miyaji, Hiromi Yamamoto, Shunichi Miyazaki
Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic β-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or β-blocker bisoprolol (BISO)...
April 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/26583148/novel-therapeutic-strategies-for-reducing-right-heart-failure-associated-mortality-in-fibrotic-lung-diseases
#20
REVIEW
Ayodeji Adegunsoye, Matthew Levy, Olusegun Oyenuga
Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors...
2015: BioMed Research International
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