title: [The Action of Apelin-12 and Its Analog on Hemodynamics and Cardiac Contractile Function of Rats With Isoproterenol-Induced Myocardial Lesion].
abstract: Introduction of isoproterenol (beta-adrenoreceptor agonist) into rats is one of the widespread experimental models of heart failure. It is caused by diffuse ischemic damage of cardiomyocytes, followed by development of substitutive fibrosis. Apelin is a natural regulator of the myocardial contractility. The effects of apelin molecule fragment, apelin-12 and its more stable synthetic analogue, apelin-12-2 on cardiac contractile function of rats with isoproterenol-induced myocardial lesion (IML) and control animals has been studied in this work using invasive (catheterization of the left ventricle) and non-invasive (echocardiography and impedansometry) methods. Infusion of both peptides was made by sequentially increasing rate from 0.5 to 50 µg/kg/min. In the control group, efficacy of apelin-12 was low while apelin-12-2 moderately but significantly increased indices of myocardial contractility and relaxability. These changes were more pronounced in rats with IML and, in addition, the heart rate and LV systolic pressure increased in this group. These results correlate well with echocardiographic studies which showed increases of LV end diastolic volume, stroke volume and ejection fraction by 17-38%. These alterations are probably due to improved Ca2+ transport in cardiomyocytes, as in experiments on isolated cardiomyocytes both apelins have facilitated and improved Ca2+ removal from myoplasma. The results allow to conclude that apelin-12-2 seems to be a promising candidate for further development as a therapeutic agent in heart failure.
authors.forename: V L
authors.initials: VL
authors.lastname: Lakomkin
authors.forename: A A
authors.initials: AA
authors.lastname: Abramov
authors.forename: E V
authors.initials: EV
authors.lastname: Lukoshkova
authors.forename: S V
authors.initials: SV
authors.lastname: Lakomkin
authors.forename: V V
authors.initials: VV
authors.lastname: Gramovich
authors.forename: O N
authors.initials: ON
authors.lastname: Vyborov
authors.forename: N A
authors.initials: NA
authors.lastname: Undrovinas
authors.forename: V V
authors.initials: VV
authors.lastname: Ermishkin
authors.forename: V G
authors.initials: VG
authors.lastname: Tsyplenkova
authors.forename: V P
authors.initials: VP
authors.lastname: Shirinsky
authors.forename: V I
authors.initials: VI
authors.lastname: Kapelko
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C495200:apelin-12 peptide; D007545:Isoproterenol