Anti-inflammatory properties of azelnidipine, a dihydropyridine-based calcium channel blocker.
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.
Komoda
Hiroshi
H
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
Inoue
Teruo
T
Node
Koichi
K
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
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