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 microg/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.
Highlights
Aldosterone-high salt intake produces a variety of deleterious actions on the cardiovascular system of uninephrectomized rats
Systolic blood pressure increased in both the ALDO and ALDOF groups indicating a non-antihypertensive effect of felodipine
We have demonstrated that felodipine given to aldosterone-high salt uninephrectomized rats prevents arterial inflammation, myocyte necrosis, myocardial fibrosis, and renal dysfunction
Summary
Aldosterone-high salt intake produces a variety of deleterious actions on the cardiovascular system of uninephrectomized rats. The mechanisms by which aldosterone induces cardiac tissue damage are not fully understood and seem to involve genomic and non-genomic effects [4]. Genomic action is the classical mechanism by which aldosterone binds to mineralocorticoid receptors (MR) and promotes protein synthesis. Non-genomic effects of aldosterone occur within minutes, inducing vasoconstriction [5]. Vascular smooth muscle cells from spontaneously hypertensive rats show an increased aldosterone-induced non-genomic signaling mediated by c-Src. vascular smooth muscle cells from spontaneously hypertensive rats show an increased aldosterone-induced non-genomic signaling mediated by c-Src This signaling appears to be important in the profibrotic and proinflammatory actions of aldosterone in this genetic model of hypertension [6]
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