Beneficial effects of low-dose benidipine in acute autoimmune myocarditis: suppressive effects on inflammatory cytokines and inducible nitric oxide synthase.
Excessive production of nitric oxide (NO) by inducible NO synthase (iNOS) contributes to the progression of myocardial damage in myocarditis. Some dihydropyridine calcium channel blockers reportedly inhibit NO production and proinflammatory cytokines and the present study sought to clarify if a low dose of benidipine, a novel dihydropyridine calcium channel blocker, would ameliorate experimental autoimmune myocarditis (EAM). Rats with or without myocarditis were administered oral benidipine at a dose of 3 mg. kg(-1). day(-1) for 3 weeks. Low-dose benidipine did not decrease blood pressure significantly compared with the untreated group, but markedly reduced the severity of myocarditis. Myocardial interleukin-1beta (IL-1beta) expression and IL-1beta-positive cells were significantly less in rats with EAM that were treated with low-dose benidipine compared with untreated rats. Also, myocardial iNOS expression and iNOS-positive cells were markedly reduced in in the treated rats compared with the untreated group. Furthermore, myocardial NO production and nitrotyrosine expression were suppressed by the treatment in rats with EAM. The cardioprotection of low-dose benidipine may be caused by suppression of inflammatory cytokines and inhibition of NO production.
Yuan
Zuyi
Z
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Kishimoto
Chiharu
C
Shioji
Keisuke
K
D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate / Q000187:drug effects; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016207:Cytokines; D004095:Dihydropyridines; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C061004:benidipine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat