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 microM), lansoprazole (100-300 microM) and SCH 28080 (10-100 microM) 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 microM), propranolol (15 microM), atropine (1 microM), ouabain (2 microM), theophylline (300 microM) and milrinone (100 microM). 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 microM) 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.
Yenisehirli
Aydan
A
Department of Pharmacology, Faculty of Medicine, Gaziosmanpasa University, Tokat 60100, Turkey. aydany@hacettepe.edu.tr
Onur
Rustu
R
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D064747:Lansoprazole; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013806:Theophylline / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D054328:Proton Pump Inhibitors; C035235:Sch 28080; D064747:Lansoprazole; D010042:Ouabain; D013806:Theophylline; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D020105:Milrinone; D009853:Omeprazole