title: Interaction of atrial natriuretic peptide and ouabain in the myocardium.
abstract: Natriuretic peptides and digitalis-like compounds serve as regulators of homeostasis, including control of volume expansion and blood pressure. The aim of the present study was to explore possible interactions between atrial natriuretic peptide (ANP) and ouabain in the heart. ANP (1 nmol/L) had no effect in papillary muscle preparations from guinea pigs. Ouabain (1 µmol/L) induced positive inotropic effect. The addition of ANP prior to ouabain resulted in a significant decrease in the ouabain-induced positive inotropic effect, manifested as an attenuated increase in twitch maximal upward force slope and resting muscular tension. In addition, ANP caused an increase in Na⁺-K⁺-ATPase activity in heart microsomal preparations. The effect of ouabain on Na⁺-K⁺-ATPase activity was shown in a biphasic manner. Ouabain (0.01-1 nmol/L) had a small but significant increase on pump activity, but higher doses of ouabain inhibited activity. ANP attenuated ouabain-induced Na⁺-K⁺-ATPase activity. Furthermore, ouabain (50 nmol/L) or ANP (10 nmol/L) alone induced Akt activation in cardiomyocytes. However, ANP blocked ouabain-induced Akt activation. These results point to the existence of interactions between ANP and ouabain on Na⁺-K⁺-ATPase signaling and function in the heart, which may be mediated by regulation of Na⁺-K⁺-ATPase activity and (or) signal transduction mechanisms.
authors.affiliation: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Maoz
authors.initials: M
authors.lastname: Nesher
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Daxiang
authors.initials: D
authors.lastname: Li
authors.forename: Haim
authors.initials: H
authors.lastname: Rosen
authors.forename: David
authors.initials: D
authors.lastname: Lichtstein
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009129:Muscle Tonus / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D010042:Ouabain; D009320:Atrial Natriuretic Factor; D051057:Proto-Oncogene Proteins c-akt; D000254:Sodium-Potassium-Exchanging ATPase