Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats.
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.
Matsubara
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BB
Departamento de Clínica Médica, Universidade Estadual Paulista, Botucatu, SP, Brasil. beatrizm@fmb.unesp.br <beatrizm@fmb.unesp.br>
Franco
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Janicki
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JS
Matsubara
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D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015736:Felodipine / Q000627:therapeutic use*; D005355:Fibrosis / Q000517:prevention & control; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis / Q000517:prevention & control; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride
D002121:Calcium Channel Blockers; D012965:Sodium Chloride; D000450:Aldosterone; D015736:Felodipine