title: Positive Inotropic Effect of Prostaglandin F2α in Rat Ventricular Trabeculae.
abstract: Prostaglandins are ubiquitous signaling molecules in the body that produce autocrine/paracrine effects on target cells in response to mechanical or chemical signals. In the heart, long-term exposure to prostaglandin (PG) F2α has been linked to the development of hypertrophy; however, there is no consensus on the acute effect of PGF2α. Our aim was to determine the response to exogenous PGF2α in isolated trabeculae from rat hearts. PGF2α (1 μM) increased both the Ca transients and the isometric stress in trabeculae, reaching steady state after 10-15 minutes, without altering the time course of Ca transient decay. The precursor of PGF2α, arachidonic acid, also stimulated a similar response. The positive inotropic effect of PGF2α was mediated through a protein kinase C signaling pathway that involved activation of the sarcolemmal Na/H exchanger. We also found that the slow force response to stretch was attenuated in the presence of PGF2α and by addition of indomethacin, a blocker of prostaglandin synthesis. In conclusion, PGF2α was positively inotropic when acutely applied to trabeculae and contributed to the increased Ca transients during the slow force response to stretch. Together, these data suggest that PGF2α is important in maintaining homeostasis during volume loading in healthy hearts.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Sarbjot
authors.initials: S
authors.lastname: Kaur
authors.forename: Amelia
authors.initials: A
authors.lastname: Power
authors.forename: Logan Z J
authors.initials: LZ
authors.lastname: Williams
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Ward
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D016861:Cyclooxygenase Inhibitors; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D016718:Arachidonic Acid; C093373:cariporide; D015237:Dinoprost; D011493:Protein Kinase C; D007213:Indomethacin