Proton pump inhibitors omeprazole and lansoprazole induce relaxation of isolated human arteries.
Vasorelaxant effects of H+/K+-ATPase were previously demonstrated in artery rings isolated from experimental animals. We examined the effects of clinically used H+/K+-ATPase inhibitors on isolated human internal mammary (n=19) and radial (n=5) arteries. Omeprazole and lansoprazole (30-300 microM) both induced concentration-dependent, reversible and reproducible relaxations of arteries which were precontracted with phenylephrine (5 microM), histamine (15 microM), high K+ (80 mM), ouabain (1 microM) and K+ free solution. Relaxant responses were similar in both arteries. Presence of Nomega-Nitro-L-arginine methyl ester (30 microM) had no effect on lansoprazole-induced responses, thus relaxations are independent from nitric oxide. Relaxation in the K+ free medium implies that this action could not be due to the inhibition of H+/K+-ATPase. Lansoprazole (300 microM) inhibited Ca2+-induced contractions in high K+-Ca2+ free medium. Omeprazole and lansoprazole may act on a common mechanism which plays a crucial role in regulating human vascular tone and that mechanism appeared to be involved in the regulation of intracellular Ca2+.
Naseri
Erdinc
E
Department of Cardiovascular Surgery, Faculty of Medicine, Gaziosmanpasa University, Tokat 60100, Turkey.
Yenisehirli
Aydan
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000368:Aged; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D064747:Lansoprazole; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D017534:Radial Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D014662:Vasoconstrictor Agents; D064747:Lansoprazole; D010656:Phenylephrine; D009569:Nitric Oxide; D010042:Ouabain; D006632:Histamine; D019001:Nitric Oxide Synthase; D009853:Omeprazole; D011188:Potassium; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester