title: Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system.
abstract: Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.
authors.affiliation: Department of Pharmacology, University of Zagreb Medical School, Salata 11, 10000 Zagreb, Croatia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Balenovic
authors.forename: Martina Lovric
authors.initials: ML
authors.lastname: Bencic
authors.forename: Mario
authors.initials: M
authors.lastname: Udovicic
authors.forename: Karol
authors.initials: K
authors.lastname: Simonji
authors.forename: Jadranka Separovic
authors.initials: JS
authors.lastname: Hanzevacki
authors.forename: Ivan
authors.initials: I
authors.lastname: Barisic
authors.forename: Stjepan
authors.initials: S
authors.lastname: Kranjcevic
authors.forename: Ingrid
authors.initials: I
authors.lastname: Prkacin
authors.forename: Vedran
authors.initials: V
authors.lastname: Coric
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Marijana
authors.initials: M
authors.lastname: Coric
authors.forename: Iva
authors.initials: I
authors.lastname: Brcic
authors.forename: Suzana
authors.initials: S
authors.lastname: Borovic
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Vrcic
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008520:Medigoxin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000889:Anti-Arrhythmia Agents; D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; C083833:BPC 157; D001120:Arginine; D008520:Medigoxin; D019331:NG-Nitroarginine Methyl Ester