• Eur. J. Pharmacol. · Feb 2015

    Prostaglandin F₂α modulates atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.

    • Vahid Nikoui, Shahram Ejtemaei Mehr, Farahnaz Jazaeri, Sattar Ostadhadi, Golnar Eftekhari, Ahmad-Reza Dehpour, Ali R Mani, and Azam Bakhtiarian.
    • Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nikoui@alumnus.tums.ac.ir.
    • Eur. J. Pharmacol. 2015 Feb 5; 748: 149-56.

    AbstractEndotoxemia 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.Copyright © 2015. Published by Elsevier B.V.

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