Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

Abstract

It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1% NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg·kg -1 ·day -1 felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 ± 20) and ALDOF (168 ± 13) compared to CTL (123 ± 12) and CNEP (134 ± 13). Heart damage (lesion scores -median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction (%) in ALDOF (2.9 ± 0.5) was similar to CTL (2.9 ± 0.5) and CNEP (3.4 ± 0.4) and decreased compared to ALDO (5.1 ± 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

“…Another research showed that after unilateral nephrectomy rats received high dose of aldosterone (0.75 μg/h) via implanted minipump for 4 weeks, perivascular fibrosis was first detected in the experimental group [140]. However, Matsubara et al observed perivascular fibrosis in the sixth week by using the same method [141].…”

Aldosterone is associated with left ventricular hypertrophy in hemodialysis patients

“…It has been known that aldosterone is associated with abnormal myocardial growth [Matsubara et al 2010]. Besides sodium retention, aldosterone also reduces myocardial norepinephrine uptake and sensitivity of baroreceptors, promotes myocardial fibrosis, fibroblast proliferation, and changes in sodium channel expression [Rocco and Fang, 2006].…”