title: Effects of the dihydropyridine calcium channel blocker amlodipine on ventricular and atrial protein synthesis in an aortic constriction model of hypertension and, following chronic treatment, in the left ventricle of SHR rats.
abstract: The dihydropyridine calcium channel blocking agent amlodipine is an effective anti-hypertensive agent and its use (in doses of 5 or 10 mg/day/kg body weight) was investigated in male Wistar rats with hypertension induced by aortic constriction. Controls were sham-operated and pair-fed. At the end of the study, rates of protein synthesis were measured with radiolabelled phenylalanine to calculate fractional rates of protein synthesis (ks), absolute rates of protein synthesis (Vs) and synthesis rates relative to RNA (kRNA). After 30 days of aortic constriction, weights of the left ventricle and left atrium were significantly increased by hypertension. The weights of the right ventricle and right atrium were relatively unaffected. Hypertension was accompanied by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protein contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fraction, ks decreased. The right ventricle and right atrium were generally unaffected except for a decline in mixed protein ks. Many of these changes in hypertension were ameliorated by treatment with amlodipine, particularly at the higher dose (i.e. 10 mg/kg body weight/day) implicating an effect on protein metabolism. In the left ventricle these included amelioration of the increases in mixed and contractile proteins, total RNA contents, mixed Vs and Vs for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hypertension-induced reduction in right ventricule rates of protein synthesis. Although the preceding study emphasises the preventative aspects of amlodipine's efficacy, an additional study was carried out in SHR rats to ascertain the applicability for regression per se. Amlodipine (10 mg/kg/body weight) therapy for 30 weeks caused regression of LV mass, total protein, RNA and DNA contents. We conclude that amlodipine, is an efficient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model.
authors.affiliation: Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK.
authors.forename: V B
authors.initials: VB
authors.lastname: Patel
authors.forename: T
authors.initials: T
authors.lastname: Siddiq
authors.forename: R
authors.initials: R
authors.lastname: Sherwood
authors.forename: P J
authors.initials: PJ
authors.lastname: Richardson
authors.forename: V R
authors.initials: VR
authors.lastname: Preedy
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003285:Contractile Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006325:Heart Atria / Q000187:drug effects* / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D006973:Hypertension / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D003285:Contractile Proteins; D009124:Muscle Proteins; D017311:Amlodipine