Back to Search
Start Over
Spironolactone ameliorates arterial medial calcification in uremic rats: the role of mineralocorticoid receptor signaling in vascular calcification.
Spironolactone ameliorates arterial medial calcification in uremic rats: the role of mineralocorticoid receptor signaling in vascular calcification.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2015 Dec 01; Vol. 309 (11), pp. F967-79. Date of Electronic Publication: 2015 Sep 02. - Publication Year :
- 2015
-
Abstract
- Vascular calcification (VC) is a critical complication in patients with chronic kidney disease (CKD). The effects of spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, on VC have not been fully investigated in CKD. The present in vivo study determined the protective effects of SPL on VC in CKD rats. Rats were divided into a control group and four groups of rats with adenine-induced CKD. Three groups were treated with 0, 50, and 100 mg·kg(-1)·day(-1) SPL for 8 wk, and one group was treated with 100 mg·kg(-1)·day(-1) SPL for the last 2 wk of the 8-wk treatment period. After 8 wk, CKD rats developed azotemia and hyperphosphatemia, with increases in the expression of serum and glucocorticoid-regulated kinase-1 and sodium-phosphate cotransporter, in inflammation and oxidative stress level, in osteogenic signaling and apoptosis, and in aortic calcification, compared with control rats. SPL dose dependently decreased these changes in the aortas, concomitant with improvements in renal inflammation, tubulointerstitial nephritis, and kidney function. SPL neither lowered blood pressure level nor induced hyperkalemia. Treatment of CKD rats for the last 2 wk with 100 mg·kg(-1)·day(-1) SPL attenuated VC compared with CKD rats with the same degree of kidney function and hyperphosphatemia. In conclusion, SPL dose dependently inhibits the progression of VC by suppressing MR signaling, local inflammation, osteogenic transition, and apoptosis in the aortas of CKD rats.<br /> (Copyright © 2015 the American Physiological Society.)
- Subjects :
- Adenine
Animals
Aorta, Abdominal metabolism
Aorta, Abdominal pathology
Aortic Diseases blood
Aortic Diseases chemically induced
Aortic Diseases pathology
Aortic Diseases physiopathology
Apoptosis drug effects
Biomarkers blood
Disease Models, Animal
Disease Progression
Dose-Response Relationship, Drug
Humans
Hyperphosphatemia blood
Hyperphosphatemia drug therapy
Kidney drug effects
Kidney metabolism
Kidney pathology
Kidney physiopathology
Male
Osteogenesis drug effects
Rats, Sprague-Dawley
Receptors, Mineralocorticoid metabolism
Renal Insufficiency, Chronic blood
Renal Insufficiency, Chronic chemically induced
Renal Insufficiency, Chronic pathology
Renal Insufficiency, Chronic physiopathology
Renin-Angiotensin System drug effects
Signal Transduction drug effects
Time Factors
Tunica Media metabolism
Tunica Media pathology
Uremia blood
Uremia chemically induced
Uremia pathology
Uremia physiopathology
Vascular Calcification blood
Vascular Calcification chemically induced
Vascular Calcification pathology
Vascular Calcification physiopathology
Aorta, Abdominal drug effects
Aortic Diseases prevention & control
Mineralocorticoid Receptor Antagonists pharmacology
Receptors, Mineralocorticoid drug effects
Renal Insufficiency, Chronic drug therapy
Spironolactone pharmacology
Tunica Media drug effects
Uremia drug therapy
Vascular Calcification prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 309
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 26336165
- Full Text :
- https://doi.org/10.1152/ajprenal.00669.2014