title: Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.
abstract: Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal.
authors.affiliation: Laboratorio de Farmacognosia y Farmacología, Facultad de Farmacia, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca 37007, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Sevilla
authors.forename: Felipe
authors.initials: F
authors.lastname: Voces
authors.forename: Rosalía
authors.initials: R
authors.lastname: Carrón
authors.forename: Estela I
authors.initials: EI
authors.lastname: Guerrero
authors.forename: Noelia
authors.initials: N
authors.lastname: Ardanaz
authors.forename: Luis
authors.initials: L
authors.lastname: San Román
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Arévalo
authors.forename: María J
authors.initials: MJ
authors.lastname: Montero
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018715:Microscopy, Video; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020127:Recovery of Function
chemical_list: D000959:Antihypertensive Agents; D017311:Amlodipine