title: Prostaglandin F₂α modulates atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.
abstract: Endotoxemia induces various physiological adaptive responses such as tachycardia. There is evidence to show that inflammatory tachycardia might be linked to a direct action of prostanoids on the cardiac pacemaker cells. Recent reports have indicated that systemic inflammation may uncouple of cardiac pacemaker from cholinergic neural control in experimental animals; however, the exact mechanism of this phenomenon is uncertain. This study was aimed to explore the hypothesis that prostanoids modulate atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats. Male albino rats were given intraperitoneal injection of either saline or lipopolysaccharide (LPS, 1 mg/kg). 3 h after saline or LPS injection, the atria were isolated and chronotropic responsiveness to cholinergic stimulation was evaluated in an organ bath. The expression of atrial cyclooxygenases (COX)-1, COX-2 and COX-3 mRNA was assessed by quantitative real-time RT-PCR and cytosocalcium-dependent phospholipase A₂ (cPLA₂) activity was measured in the atria. The expression of atrial COX-2 mRNA and cPLA₂ activity increased significantly in endotoxemic atria (P<0.05). Incubation with prostaglandin F₂α (PGF₂α, 100 pM) could significantly decrease chronotropic response to cholinergic stimulation in vitro. Likewise, LPS injection could induce a significant hyporesponsiveness to cholinergic stimulation, and incubation of isolated atria with either indomethacin (5 µM) or AL-8810 (a PGF₂α antagonist, 10 µM) could reverse it (P<0.01, P<0.05, respectively), while SQ29548 (a thromboxane A₂ antagonist, 10 nM) was failed (P>0.05). Our data showed that PGF₂α may contribute to the atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nikoui@alumnus.tums.ac.ir.
authors.forename: Vahid
authors.initials: V
authors.lastname: Nikoui
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ejtemam@tums.ac.ir.
authors.forename: Shahram
authors.initials: S
authors.lastname: Ejtemaei Mehr
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: fjazaeri@yahoo.com.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Jazaeri
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ostadhadi@razi.tums.ac.ir.
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: golnar.eftekhari@yahoo.com.
authors.forename: Golnar
authors.initials: G
authors.lastname: Eftekhari
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.
authors.forename: Ahmad-Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: mani@modares.ac.ir.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Mani
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: bakhtiar@tums.ac.ir.
authors.forename: Azam
authors.initials: A
authors.lastname: Bakhtiarian
mesh_terms: D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology*; D019446:Endotoxemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011982:Receptors, Prostaglandin / Q000235:genetics; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics
chemical_list: D018678:Cholinergic Agents; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D054510:Phospholipases A2, Cytosolic
keywords: AL-8810 (PubChem CID: 5311238); Chronotropic response; Cyclooxygenase; Endotoxin; Ethanol (PubChem CID: 702); I-BOP (PubChem CID: 5311175); Indomethacin (PubChem CID: 3715); PGF(2α) (PubChem CID: 20849107); PLA(2); Prostaglandin F(2α); SQ29548 (PubChem CID: 6437074); Systemic inflammation