title: Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.
abstract: Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Honda
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohara
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Katagi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143-8540, Japan. Electronic address: atsushi.sugiyama@med.toho-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D018685:Anesthetics, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006221:Halothane; D006339:Heart Rate / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D020105:Milrinone / Q000494:pharmacology; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; C461399:ONO-AE1-329; D058309:Receptors, Prostaglandin E, EP4 Subtype; D004280:Dobutamine; D020105:Milrinone; D006221:Halothane; D004298:Dopamine
keywords: Catecholamines; Diastolic dysfunction; EP4; ONO-AE1-329; ONO-AE1-329 (PubChem CID: 5311230); Phosphodiesterase 3 inhibitor; Pressure-volume relationship