Effect of different dihydropyridine-type Ca2+ antagonists on left ventricle hypertrophy and coronary changes in spontaneously hypertensive rats.
Effects of treatment with equi-hypotensive doses of first-, second-, and third-generation dihydropyridine-type Ca2+ channel blockers on hypertension-dependent left ventricle hypertrophy and coronary vascular changes were assessed in spontaneously hypertensive rats (SHRs) by quantitative microanatomic techniques. Male SHRs were treated for 12 weeks with equi-hypotensive doses of nifedipine, isradipine, manidipine, amlodipine, and lercanidipine. Untreated age-matched normotensive Wistar-Kyoto rats were used as a reference group. Compounds investigated decreased to a similar extent systolic pressure in SHRs. Increased cardiocyte size (hypertrophy), development of necrosis and fibrosis areas, and increased thickness of coronary arteries with luminal narrowing were observed in control SHRs. Pharmacologic treatment countered hypertension-dependent left ventricle and coronary artery changes in SHRs. Manidipine, amlodipine, and lercanidipine displayed a similar activity, whereas nifedipine and isradipine were less potent. These findings support observations that antihypertensive treatment counters hypertension-related left ventricle and coronary changes. The observation of a different effect of Ca2+ antagonists tested suggests the possibility of a more favorable cardiac profile exerted by some dihydropyridines. The evaluation of specific properties of dihydropyridines on hypertensive end-organ damage may contribute to better choices depending on clinical situations.
Tomassoni
Daniele
D
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Italy.
Sabbatini
Maurizio
M
Amenta
Francesco
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D004095:Dihydropyridines