EFFICIENT INHIBITION OF THE DEVELOPMENT OF CARDIAC REMODELING BY A LONG-ACTING CALCIUM-ANTAGONIST AMLODIPINE

The purpose of the present study was to examine the effects oi a long- acting calcium antagonist, amlodipine, on the development of cardiac r emodeling. Dihydropyridine calcium antagonists have been used widely f or many years in the treatment of hypertension and angina pectoris. It has been reported, however, that a prototype of dihydropyridines, nif edipine, does not reduce mortality of patients with ischemic heart dis ease, possibly because of reflex stimulation of the sympathetic nervou s system. A calcium antagonist, amlodipine, has been reported to have potential benefits by virtue of a gradual onset of action and a long d uration of effects. Amlodipine (8 mg/kg per day, once a day) or nifedi pine (24 mg/kg per day, three times a day) was administered to spontan eously hypertensive 12-week-old rats for 12 weeks. Left ventricular wa ll thickness was measured by echocardiography, and relative amounts of myosin heavy chain isoforms were assessed by pyrophosphate gels. Expr essions of ''fetal type'' genes and type 1 collagen gene were examined by Northern blot analysis, Amlodipine and nifedipine both markedly re duced systolic blood pressure. However, the decrease in systolic blood pressure caused by nifedipine continued for no more than 8 hours, whe reas the blood pressure-lowering effect of amlodipine continued for mo re than 16 hours post dose. Amlodipine markedly reduced left ventricul ar wall thickness, whereas nifedipine only weakly attenuated an increa se in the wall thickness, Amlodipine, but not nifedipine, prevented an increase in the relative amount of V3 myosin heavy chain isoform and suppressed an increase in mRNA levels of beta-myosin heavy chain, skel etal alpha-actin, and type 1 collagen. Unlike nifedipine, amlodipine e ffectively preveted cardiac remodeling secondary to high blood pressur e at biochemical levels and morphological levels. These results sugges t that a long-acting calcium antagonist is more effective thana short- acting one in preventing organ injury in hypertensive subjects.