title: Prophylactic effects of an N- and L-type Ca2+ antagonist, cilnidipine, against cardiac hypertrophy and dysfunction in stroke-prone, spontaneously hypertensive rats.
abstract: To clarify the beneficial effects of cilnidipine, an L- and N-type calcium channel blocker, which were clinically observed against diastolic dysfunction in hypertrophied hearts of hypertensive patients, we investigated the effects of cilnidipine on cardiac remodeling and enhanced gene expression in stroke-prone, spontaneously hypertensive rats in comparison with that of captopril, a well-known angiotensin-converting enzyme inhibitor, at threshold doses with little blood pressure lowering effect. The expression of type III collagen and beta/alpha-myosin heavy chain as well as transforming growth factor-beta, and basic fibroblast growth factor were suppressed by both treatments, indicating the prevention or amelioration of cardiac dysfunction. Such beneficial effects were much more intense with cilnidipine treatment than in captopril. These results indicate that Ca2+ is a key factor in the pathogenesis of cardiac remodeling in hypertension. One possible beneficial effect of cilnidipine in the prevention of cardiac dysfunction may be due to the decreased amount of growth factors such as transforming growth factor-beta and basic fibroblast growth factor via direct action for Ca2+ influx and also via inhibition of local renin-angiotensin system in the myocardium.
authors.affiliation: Department of Pathology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takemori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishida
authors.forename: Kensaku
authors.initials: K
authors.lastname: Dote
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use; D006332:Cardiomegaly / Q000378:metabolism / Q000517:prevention & control; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004095:Dihydropyridines / Q000627:therapeutic use*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000150:complications / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D024061:Collagen Type III; D004095:Dihydropyridines; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C065927:cilnidipine; D002216:Captopril; D024723:Ventricular Myosins