Positive inotropic and negative chronotropic effects of proton pump inhibitors in isolated rat atrium

The effects of three specific H+/K+-ATPase inhibitors (omeprazole, lansoprazole and SCH 28080 (2-methyl-8-(phenylmethoxy)-imidazo[1,2-a] pyridine-3-acetonitrile)) were investigated on the mechanical and electrophysiological properties of rat atrium, in vitro. Omeprazole (100-300 μM), lansoprazole (100-300 μM) and SCH 28080 (10-100 μM) increased the amplitude of contractions and decreased the beating rate. These effects are reversible, reproducible and correlated with their order of potency as gastric H+/K+-ATPase inhibitors; SCH 28080 > omeprazole = lansoprazole. Cardiac effects of proton pump inhibitors were not inhibited with phentolamine (5 μM), propranolol (15 μM), atropine (1 μM), ouabain (2 μM), theophylline (300 μM) and milrinone (100 μM). Ouabain-induced increase in beating rate and contracture development were antagonized by H+/K+-ATPase inhibitors. Ouabain increased the positive inotropic effect of H+/K+-ATPase inhibitors. Lansoprazole (300 μM) significantly prolonged the duration of action potentials in rat atrial cells. H+/K+-ATPase may play a crucial role in the mechanical and electrophysiological properties of rat atrial myocardium.