التفاصيل البيبلوغرافية
| العنوان: |
Effects of Mineralocorticoid Receptor Blockade and Statins on Kidney Injury Marker 1 (KIM-1) in Female Rats Receiving L-NAME and Angiotensin II |
| المؤلفون: |
Jiayan Huang, Ezgi Caliskan Guzelce, Shadi K. Gholami, Kara L. Gawelek, Richard N. Mitchell, Luminita H. Pojoga, Jose R. Romero, Gordon H. Williams, Gail K. Adler |
| المصدر: |
International Journal of Molecular Sciences; Volume 24; Issue 7; Pages: 6500 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
N-omega-nitro-L-arginine methyl ester (L-NAME), angiotensin II (ANG II), mineralocorticoid receptor (MR), statin, simvastatin, pravastatin, kidney injury molecule (KIM-1), CVD (cardiovascular disease) |
| جغرافية الموضوع: |
agris |
| الوصف: |
Kidney injury molecule-1 (KIM-1) is a biomarker of renal injury and a predictor of cardiovascular disease. Aldosterone, via activation of the mineralocorticoid receptor, is linked to cardiac and renal injury. However, the impact of mineralocorticoid receptor activation and blockade on KIM-1 is uncertain. We investigated whether renal KIM-1 is increased in a cardiorenal injury model induced by L-NAME/ANG II, and whether mineralocorticoid receptor blockade prevents the increase in KIM-1. Since statin use is associated with lower aldosterone, we also investigated whether administering eiSther a lipophilic statin (simvastatin) or a hydrophilic statin (pravastatin) prevents the increase in renal KIM-1. Female Wistar rats (8–10 week old), consuming a high salt diet (1.6% Na+), were randomized to the following conditions for 14 days: control; L-NAME (0.2 mg/mL in drinking water)/ANG II (225 ug/kg/day on days 12–14); L-NAME/ANG II + eplerenone (100 mg/kg/day p.o.); L-NAME/ANG II + pravastatin (20 mg/kg/day p.o.); L-NAME/ANG II + simvastatin (20 mg/kg/day p.o.). Groups treated with L-NAME/ANG II had significantly higher blood pressure, plasma and urine aldosterone, cardiac injury/stroke composite score, and renal KIM-1 than the control group. Both eplerenone and simvastatin reduced 24-h urinary KIM-1 (p = 0.0046, p = 0.031, respectively) and renal KIM-1 immunostaining (p = 0.004, p = 0.037, respectively). Eplerenone also reduced renal KIM-1 mRNA expression (p = 0.012) and cardiac injury/stroke composite score (p = 0.04). Pravastatin did not affect these damage markers. The 24-h urinary KIM-1, renal KIM-1 immunostaining, and renal KIM-1 mRNA expression correlated with cardiac injury/stroke composite score (p < 0.0001, Spearman ranked correlation = 0.69, 0.66, 0.59, respectively). In conclusion, L-NAME/ANG II increases renal KIM-1 and both eplerenone and simvastatin blunt this increase in renal KIM-1. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms24076500 |
| DOI: |
10.3390/ijms24076500 |
| الاتاحة: |
https://doi.org/10.3390/ijms24076500 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.D473752A |
| قاعدة البيانات: |
BASE |