title: Effects of peripherally administered urotensin II and arginine vasotocin on the QT interval of the electrocardiogram in trout.
abstract: The QT interval of the electrocardiogram (ECG) is a measure of the duration of the ventricular depolarization and repolarization. In fish as in human, the QT interval is positively correlated with the RR interval of the ECG, a measure of the cardiac cycle length. Urotensin II (UII) is a neuropeptide that has been highly conserved from fish to human, and UII and its receptor (UT) are expressed in cardiovascular tissues including the heart. Although UII exerts potent cardiovascular actions, its possible effects on the QT interval have never been investigated. The goal of the present study was to provide insight into the potential effect of UII on the QT interval in an established in vivo trout model. To this end, the effects of UII on dorsal aortic blood pressure (PDA), RR, QT intervals and corrected QT (QTc) for RR interval, were investigated after intra-arterial (IA) injection of 5, 50 and 100 pmol UII. The effects of UII were compared to those of two structurally UII-related peptides (URPs), URP1 and URP2, and to those of arginine vasotocin (AVT), homolog of the mammalian arginine vasopressin. IA injection of vehicle or 5 pmol UII had no effect on the various parameters. At the 50-pmol dose, UII evoked its usual increase in PDA with a peak value observed 15 min after the injection (+22% from baseline, P<0.001). This hypertensive effect of UII was accompanied by a significant increase in the RR interval (+18%, P<0.001), i.e. a bradycardia, and these effects remained constant until the end of the recording. The highest dose of UII evoked similar hypertensive and bradycardic effects. Of interest, the QT interval did not change during the bradycardic action of UII (50 and 100 pmol) but the QTc interval significantly decreased. In trout pre-treated with urantide, a peptidic antagonist of UT, the hypertensive and bradycardic actions of 50 pmol UII were reduced 3-fold and no change occurred in the QT and QTc intervals. In trout pre-treated with blockers of the autonomic nervous system, the hypertensive effect of UII was maintained but no change appeared in RR, QT and QTc intervals. IA injections of 50 pmol URPs were without action on the preceding parameters. IA administration of 50 pmol AVT provoked quite similar increase in PDA, and elevation of the RR interval to those evoked by IA injection of UII but, in contrast to UII, AVT injection induced a highly significant and sustained prolongation of the QT interval compared to baseline (+7%, P<0.001) without change in QTc. Our results are indicative of a lack of QT interval change during UII-evoked bradycardia but not after AVT-induced bradycardia and suggest for the first time that some compensatory mechanism specific for the UII peptide is working to stabilize the QT interval. Further research is needed to elucidate the mechanism involved in this action of UII. The potential for UII to prevent detrimental prolongation of cardiac ventricular repolarization might be questioned.
authors.affiliation: INSERM UMR1101, Laboratoire de Neurophysiologie, SFR ScInBioS, Université de Brest, France.
authors.forename: Gilmer
authors.initials: G
authors.lastname: Vanegas
authors.affiliation: INSERM UMR1101, Laboratoire de Neurophysiologie, SFR ScInBioS, Université de Brest, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lancien
authors.affiliation: INSERM U982, UA CNRS, Différenciation et Communication Neuronale et Neuroendocrine, Université de Rouen, Mont-Saint-Aignan, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.affiliation: INSERM U982, UA CNRS, Différenciation et Communication Neuronale et Neuroendocrine, Université de Rouen, Mont-Saint-Aignan, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.affiliation: INSERM UMR1101, Laboratoire de Neurophysiologie, SFR ScInBioS, Université de Brest, France. Electronic address: jean-claude.lemevel@univ-brest.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Le Mével
mesh_terms: D000818:Animals; D017756:Aquaculture; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000506:poisoning*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015716:Electrocardiography, Ambulatory / Q000187:drug effects / Q000662:veterinary; D005260:Female; D029941:Fish Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000506:poisoning*; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D007269:Injections, Intra-Arterial; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D017686:Oncorhynchus mykiss; D010446:Peptide Fragments / Q000627:therapeutic use; D014579:Urotensins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000506:poisoning* / Q000627:therapeutic use; D014668:Vasotocin / Q000008:administration & dosage / Q000494:pharmacology / Q000506:poisoning*
chemical_list: D002316:Cardiotonic Agents; D029941:Fish Proteins; D010446:Peptide Fragments; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C029677:urotensin II; D014668:Vasotocin
keywords: Arginine vasotocin; Electrocardiogram; Fish; QT interval; RR interval; Urotensin II