Azilsartan causes natriuresis due to its sympatholytic action in kidney disease

Kidoguchi, Satoshi; Sugano, Naoki; Takane, Koki; Takahashi, Yasuhito; Morisawa, Norihiko; Yarita, Miki; Hayashi-Ishikawa, Naomi; Tokudome, Goro; Yokoo, Takashi

doi:10.1038/s41440-019-0271-1

Cited by 7 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 Effects of RASIs on ACE2 expression in disease models of various organs. Black lines, mRNA changes; red lines, protein changes kidneys of AKI, drug injury, and UUO-induced fibrosis models, [67,69,[84][85][86], and in the liver of BDL-or CCl4induced fibrosis models [103,104]. Interestingly, potent oxidative stress, fibroinflammatory changes, and mitochondrial damage are commonly found in such disease models.…”

Section: Discussionmentioning

confidence: 99%

“…In doxorubicin-treated BALB/c mice, a model of nephrotic syndrome, renal ACE2 mRNA was overexpressed and further augmented by losartan [85]. In adenine-induced CRF in WKY, ACE2 protein in the whole kidney was within the no/marginal change level and unaffected by azilsartan [86]. However, ACE2 immunointensity was increased to an overexpression level in the glomerulus or tubules, which was unchanged by azilsartan.…”

Section: Drug Injurymentioning

confidence: 98%

See 1 more Smart Citation

Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies

Kai

Niiyama

et al. 2021

Hypertens Res

View full text Add to dashboard Cite

Angiotensin-converting enzyme 2 (ACE2) protects against organ damage in hypertension and cardiovascular diseases by counter regulating the renin-angiotensin system (RAS). ACE2 is also the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the claim that RAS inhibitors (RASIs) cause ACE2 overexpression in some animal experiments, concerns have arisen that RASIs may aggravate SARS-CoV-2 infection and coronavirus disease-2019 severity in RASI-treated patients. To achieve a comprehensive review, a systematic search of MEDLINE/PubMed was conducted regarding the effects of RASIs on tissue ACE2 mRNA/protein expression in healthy animals and animal models of human diseases. We identified 88 eligible articles involving 168 experiments in the heart, kidneys, lungs, and other organs. Three of 38 experiments involving healthy animals showed ACE2 expression greater than twice that of the control (overexpression). Among 102 disease models (130 experiments), baseline ACE2 was overexpressed in 16 models (18 experiments) and less than half the control level (repression) in 28 models (40 experiments). In 72 experiments, RASIs did not change ACE2 levels from the baseline levels of disease models. RASIs caused ACE2 overexpression compared to control levels in seven experiments, some of which were unsupported by other experiments under similar conditions. In 36 experiments, RASIs reversed or prevented disease-induced ACE2 repression, yielding no or marginal changes. Therefore, ACE2 overexpression appears to be a rare rather than common consequence of RASI treatment in healthy animals and disease models. Future studies should clarify the pathophysiological significance of RASI-induced reversal or prevention of ACE2 repression in disease models.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Drug Injurymentioning

confidence: 98%

Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies

Kai

Niiyama

et al. 2021

Hypertens Res

View full text Add to dashboard Cite

show abstract

“…Candesartan increases ACE2 activity twice in diabetes [40]. In the kidney context, azilsartan [41] and lisinopril [42] did not increase renal ACE2 expression.…”

mentioning

confidence: 85%

COVID-19 and chronic kidney disease: peculiarities of treatment

Chernatska

Grek

2022

Ukr. J. Nephrol. and Dial.

View full text Add to dashboard Cite

Abstract. The present study aimed to characterize the management of patients with chronic kidney disease with concomitant COVID-19. Articles published in 2019-2021 in the PubMed, Scopus, and Google Scholar electronic databases were analyzed. As a result of this review, the following particularities of COVID-19 treatment in chronic kidney disease could be summarized. It is obligatory to continue treatment with renin-angiotensin-aldosterone system inhibitors in patients with chronic kidney disease and COVID-19. Lisinopril is considered used for avoiding the elevated renal expression of angiotensin-converting enzyme 2. Spironolactone can prevent acute lung injuries and is reasonable if the triple combination of drugs for reducing blood pressure is not effective. Low-dose rosuvastatin therapy is recommended for patients with COVID-19 and chronic kidney disease stages 3-5 treated with antiretroviral drugs such as lopinavir and ritonavir, remdesivir. Ezetimibe is reasonable to use in case of ineffective higher doses of statins and to decrease hospitalization risk.

show abstract

“…Kidoguchi et al [44] showed the natriuretic effect of Azilsartan by inhibiting the WNK4-SPAK-NCC pathway through sympathetic inhibitory activity in a model of adenine-induced chronic renal failure.…”

Section: Ncc Is Affected By Drugsmentioning

confidence: 99%

Molecular Mechanisms of Na-Cl Cotransporter in Relation to Hypertension in Chronic Kidney Disease

Liang

Shimosawa

2022

IJMS

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a common clinical disease with an increasing incidence, affecting 10 to 15% of the world’s population. Hypertension is the most common and modifiable risk factor for preventing adverse cardiovascular outcomes in patients with CKD. A survey from developed countries shows that 47% of hypertensive patients over the age of 20 have uncontrolled blood pressure (BP), and the control rate is even lower in developing countries. CKD is both a common cause of uncontrolled hypertension and a risk factor for altered sequelae. In particular, studies have demonstrated that abnormal blood-pressure patterns in CKD patients, such as non-dipping-blood-pressure patterns, are associated with a significantly increased risk of cardiovascular (CV) disease. The distal convoluted tubule (DCT) is a region of the kidney, and although only 5–10% of the sodium (Na+) filtered by the glomerulus is reabsorbed by DCT, most studies agree that Na-Cl cotransporter (NCC) in human, rabbit, mouse, and rat kidneys is the most important route of sodium reabsorption across the DCT for maintaining the homeostasis of sodium. The regulation of NCC involves a large and complex network structure, including certain physiological factors, kinases, scaffold proteins, transporter phosphorylation, and other aspects. This regulation network includes various levels. Naturally, cross-talk between the components of this system must occur in order to relay the important signals to the transporter to play its role. Knowledge of the mechanisms regulating NCC activation is critical for understanding and treating hypertension and CKD. Previous studies from our laboratory have investigated the mechanisms through which NCC is activated in several different models. In the following sections, we review the literature on the mechanisms of NCC in relation to hypertension in CKD.

show abstract

Azilsartan causes natriuresis due to its sympatholytic action in kidney disease

Cited by 7 publications

References 43 publications

Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies

Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies

COVID-19 and chronic kidney disease: peculiarities of treatment

Molecular Mechanisms of Na-Cl Cotransporter in Relation to Hypertension in Chronic Kidney Disease

Contact Info

Product

Resources

About