Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system
| Autor: | Stjepan Kranjčević, Iva Brčić, Karol Šimonji, Hrvoje Vrcic, Luka Brčić, Ingrid Prkačin, Mario Udovičić, Dijana Balenovic, Ivan Barisic, V. Corić, Jadranka Separovic Hanzevacki, Marijana Ćorić, Bozo Radic, Martina Lovrić Benčić, Domagoj Drmic, Sven Seiwerth, Suzana Borović, Predrag Sikiric |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty pentadecapeptide BPC 157 methyldigoxin arrhythmias L-NAME L-arginine rats Arginine Heart disease Physiology Clinical Biochemistry Digitalis Pharmacology Ventricular tachycardia Nitric Oxide Biochemistry Cellular and Molecular Neuroscience Endocrinology Bolus (medicine) Heart Rate Internal medicine medicine Animals Rats Wistar biology business.industry Proteins Arrhythmias Cardiac medicine.disease biology.organism_classification Anti-Ulcer Agents Peptide Fragments Rats NG-Nitroarginine Methyl Ester Medigoxin Heart failure Toxicity business Anti-Arrhythmia Agents Digitalis Toxicity |
| Zdroj: | Regulatory peptides. 156(1-3) |
| ISSN: | 1873-1686 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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