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+.