title: Anti-inflammatory properties of azelnidipine, a dihydropyridine-based calcium channel blocker.
abstract: Accumulating evidence suggests that inflammation as well as oxidative stress play essential roles in atherogenesis, progression of atherosclerosis, and plaque instability and rupture. Recent studies on available anti-hypertensive agents have focused on their anti-atherosclerotic effects over and above their blood pressure lowering action. These studies have included investigations on several types of calcium channel blockers, with several investigations indicating that a dihydropiridine-based calcium channel blocker, azelnidipine, developed in Japan, has unique anti-oxidative properties. An anti-inflammatory effect of azelnidipine has, however, yet to be established and therefore we carried out a series of in vivo and in vitro studies to investigate this possibility. This was achieved by measuring inflammatory and oxidative stress markers in 16 high risk hypertensive patients administered 16mg/day of azelnidipine. After 4 weeks of treatment, serum levels of hsCRP, IL-6, and IL-8 and urinary 8-OHdG were decreased significantly, despite blood pressure remaining unchanged. Cultures of human mononuclear leukocytes collected from six healthy volunteers showed 100 nM of azelnidipine caused significant inhibition of formyl-methyonyl leucyl phenylalanine (fMLP)-induced production of IL-8. Taken together, these results suggest that azelnidipine has anti-inflammatory effects independent of its anti-hypertensive action. As leukocytes do not possess voltage-operated calcium channels, the effect of azelnidipine in these cells appears to occur independently of an L-type calcium channel antagonizing effect.
authors.affiliation: Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Komoda
authors.forename: Teruo
authors.initials: T
authors.lastname: Inoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D050197:Atherosclerosis / Q000517:prevention & control; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000652:urine; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; C508606:CXCL8 protein, human; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D001383:Azetidinecarboxylic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D003849:Deoxyguanosine; C061679:azelnidipine