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 mu M), lansoprazole (100-300 mu M) and SCH 28080 (10-100 mu M) 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 mu M), propranolol (15 mu M), atropine (1 mu M), ouabain (2 mu M), theophylline (300 mu M) and milrinone (100 mu M). 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 mu M) 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. (c) 2005 Elsevier B.V. All rights reserved.