| RRC ID |
88436
|
| 著者 |
Hashimoto A, Takeda Y, Karashima S, Kometani M, Aono D, Demura M, Higashitani T, Konishi S, Yoneda T, Takeda Y.
|
| タイトル |
Impact of mineralocorticoid receptor blockade with direct renin inhibition in angiotensin II-dependent hypertensive mice.
|
| ジャーナル |
Hypertens Res
|
| 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.
|
| 巻・号 |
43(10)
|
| ページ |
1099-1104
|
| 公開日 |
2020-10-1
|
| DOI |
10.1038/s41440-020-0458-5
|
| PII |
10.1038/s41440-020-0458-5
|
| PMID |
32398797
|
| MeSH |
Aldosterone / urine
Amides / pharmacology
Amides / therapeutic use*
Animals
Antihypertensive Agents / pharmacology
Antihypertensive Agents / therapeutic use*
Drug Evaluation, Preclinical
Drug Therapy, Combination
Eplerenone / pharmacology
Eplerenone / therapeutic use*
Fumarates / pharmacology
Fumarates / therapeutic use*
Hypertension / drug therapy*
Hypertension / urine
Male
Mice
Mineralocorticoid Receptor Antagonists / pharmacology
Mineralocorticoid Receptor Antagonists / therapeutic use*
|
| リソース情報 |
| 実験動物マウス |
RBRC02432 |
