title: Ouabain stimulates atrial natriuretic peptide secretion via the endothelin-1/ET(B) receptor-mediated pathway in beating rabbit atria.
abstract: OBJECTIVE
  Ouabain has been reported to increase the secretion of atrial natriuretic peptide (ANP) in vitro. However, the mechanism by which ouabain increases ANP secretion is not well known. Therefore, the purpose of the present study was to investigate the underlying mechanism of ouabain-stimulated ANP secretion.
  
  
  METHODS
  A perfused beating rabbit atrial model was used. The ANP and ET-1 levels in the atrial perfusates were measured by radioimmunoassays.
  
  
  RESULTS
  Ouabain (1.0, 3.0 and 6.0 μmol/L) significantly increased atrial ANP secretion in a dose-dependent manner, while the endothelin (ET)-1 levels were increased by the higher doses (3.0 and 6.0 μmol/L) of ouabain. Ouabain-increased atrial ET-1 release was blocked by PD98059 (30.0 μmol/L), an inhibitor of mitogen-activated protein kinase (MAPK). Nifedipine (1.0 μmol/L), an inhibitor of L-type Ca(2+) channels, completely abolished ouabain-increased ANP secretion without changing the ouabain-induced atrial dynamics. KB-R7943 (3.0 μmol/L), an inhibitor of Na(+)-Ca(2+) exchangers, completely blocked the effects of ouabain-increased atrial dynamics, but did not modulate ouabain-increased ANP secretion. ET-1 significantly stimulated atrial ANP release in a dose-dependent manner. The effects of ET-1 and ouabain on ANP secretion were completely blocked by BQ788 (0.3 μmol/L), an inhibitor of ET-1 type B (ET(B)) receptors, but not by BQ123 (0.3 μM), an inhibitor of ET-1 type A receptors. Ouabain-increased atrial ANP secretion was blocked by PD98059 and indomethacin (30.0 μmol/L), an inhibitor of cyclooxygenase.
  
  
  CONCLUSIONS
  Ouabain significantly stimulated atrial ANP secretion via an ET-1-ET(B) receptor-mediated pathway involving MAPK signaling pathway activation and prostaglandin formation.
authors.affiliation: Department of Physiology, School of Basic Medical sciences, Yanbian University, Yanji 133-002, China.
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Hong
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Li
authors.forename: Da-zhi
authors.initials: DZ
authors.lastname: Ding
authors.forename: Shan-ji
authors.initials: SJ
authors.lastname: Jin
authors.forename: Xun
authors.initials: X
authors.lastname: Cui
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D009320:Atrial Natriuretic Factor; D020928:Mitogen-Activated Protein Kinases; D013890:Thiourea; D009543:Nifedipine; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D007213:Indomethacin