ArticleHypertension research : official journal of the Japanese Society of Hypertension2020
Impact of mineralocorticoid receptor blockade with direct renin inhibition in angiotensin II-dependent hypertensive mice.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Eplerenone Attenuates Hepatic Oxidative Stress and Mitochondrial Dysfunction Following Renal Ischemia-Reperfusion Injury in Rats.Advanced pharmaceutical bulletin · 2026Article
- Apathy, gait slowness, and executive dysfunction (AGED) triad: opportunities to predict and delay dementia onset.GeroScience · 2025Article
- Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice.Scientific reports · 2023Article
- Differential Role of Aldosterone and Transforming Growth Factor Beta-1 in Cardiac Remodeling.International journal of molecular sciences · 2023Article
- Molecular and Epigenetic Control of Aldosterone Synthase, CYP11B2 and 11-Hydroxylase, CYP11B1.International journal of molecular sciences · 2023Review
- Aldosterone breakthrough from a pharmacological perspective.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- DNA Methylation of the Angiotensinogen Gene,International journal of molecular sciences · 2021Review
- A primitive type of renin-expressing lymphocyte protects the organism against infections.Scientific reports · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been suggested that aldosterone breakthrough during treatment with a type 1 angiotensin II receptor (AT1R) blocker (ARB) may be an important risk factor for the progression of renal and cardiovascular disease. We examined whether the direct renin inhibitor, aliskiren caused aldosterone breakthrough in angiotensin II (Ang II)-dependent hypertensive mice. The effect of combination therapy with aliskiren and eplerenone was compared with that of therapy using renin-angiotensin system (RAS) blockade. Tsukuba hypertensive mice were treated for 12 weeks with aliskiren (30 mg/kg/day, i.p), candesartan (5 mg/kg/day, p.o), eplerenone (100 mg/kg/day, p.o) aliskiren and candesartan, aliskiren and eplerenone or candesartan and eplerenone. Blood pressure, urinary aldosterone and angiotensinogen (AGTN) excretion; plasma endothelin-1 concentration; kidney weight; urinary albumin excretion (UAE); glomerular injury; and renal messenger RNA (mRNA) levels for transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1, angiotensin-converting enzyme (ACE) and AT1R were measured. Combination therapy with aliskiren and candesartan caused a further decrease in blood pressure (p < 0.05) compared with either agent alone. Urinary aldosterone excretion was decreased significantly by 4 weeks of treatment with aliskiren or candesartan (p < 0.05). However, it was increased again by treatment with candesartan or aliskiren for 12 weeks. Combination therapy with aliskiren and eplerenone significantly decreased UAE, the glomerulosclerosis index, and PAI-1 and TGF-β1 mRNA levels compared with all other therapies (p < 0.05). Treatment with aliskiren decreased urinary aldosterone excretion at 4 weeks and increased it at 12 weeks. Combination therapy with a direct renin inhibitor and a mineralocorticoid receptor blocker may be effective for the prevention of renal injury in Ang II-dependent hypertension.
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