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Protective cardiorenal effects of spironolactone in a rodent model of polycystic kidney disease
Author(s) -
Jeewandara Thamarasee M,
Ameer Omar Z,
Boyd Rochelle,
Wyse Benjamin F,
Underwood Conor F,
Phillips Jacqueline K
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12372
Subject(s) - endocrinology , medicine , spironolactone , aldosterone , kidney , creatinine
Summary Studies were performed to examine the contribution of aldosterone to the pathogenesis of cardiovascular and renal disease in a rodent model of genetic kidney disease. Spironolactone (20 mg/kg per day) was administered in water to mixed sex L ewis P olycystic K idney ( LPK ) rats ( n = 20) and control L ewis rats ( n = 27) from 4 to 12 weeks of age. At 12 weeks of age, hypertension was reduced in female LPK rats; systolic blood pressure declined from 226.4 ± 26.8 mm H g in untreated rats and to 179.2 ± 3.2 mm H g in treated rats ( P = 0.018). No similar effect on male or control rats was found. Water consumption and urine volume were significantly greater in LPK animals than in L ewis rats, and treatment reduced both variables by ~30% in LPK animals ( P < 0.05). Proteinuria and the urinary protein‐to‐creatinine ratio were normalized in treated LPK relative to L ewis controls, and plasma creatinine levels were significantly reduced by treatment in LPK rats. Spironolactone did not alter kidney morphology in LPK rats (fibrosis or cyst size). Aortic vascular responses to noradrenaline and acetylcholine were sensitized and impaired in the LPK ( P < 0.01). Aldosterone antagonism did not alter these responses or indicators of aortic structural remodelling. There was no treatment effect on left ventricular hypertrophy or elevated cardiac messenger RNA for β‐myosin‐heavy chain and brain natriuretic peptide in the LPK rats. However, perivascular fibrosis and messenger RNA for α‐cardiac actin were normalized by spironolactone in LPK animals relative to L ewis controls. In conclusion, we have shown an important blood pressure independent effect whereby inhibition of aldosterone via spironolactone was able to retard both renal and cardiac disease progression in a rodent model of polycystic kidney disease.