[The cardioprotective effect of a new Soviet synthetic analog of the endogenous opioids in stress due to total myocardial ischemia and its mechanisms].
It was demonstrated in experiments on male Wistar rats that preliminary use of a perfusion liquid containing the synthetic tripeptide Tyr-Pro-Arg facilitates restoration of the indices of the function of isolated perfused hearts (IPH) of rats after stress caused by 30-minute total ischemia (TI) of the myocardium at 37 degrees C. Irreversible damages to the myocardium and total depression of its function were recorded in the controls in this period of TI. The optimal concentration of the preparation in the perfusion fluid providing for restoration of IPH function by 80-100% of the initial level is 3.10(-9) M. The protective effect of the preparation is preserved in preliminary (30 minutes prior to TI) intraintestinal and intragastric administration of 10 micrograms/kg. Administration of Tyr-Pro-Arg separately or together with the beta-blocking agent propranolol as well as with atropine, which blocks the vagus effect, revealed their concurrent relations at the level of the adrenergic receptors. It is concluded that the cardioprotective effect of Tyr-Pro-Arg in TI stress is determined to a great measure by its inhibiting effect on the adrenergic mechanisms of cardiac activity regulation. Experiments in which the Ca2+ concentration in the perfusion fluid was increased threefold before and after TI showed that after using Tyr-Pro-Arg the IPH function after TI was restored and stimulated sharply by the increased Ca2+ concentration, in contrast to the controls in which stimulation of cardiac activity before TI increased the ischemic damage to the myocardium.
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D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D002317:Cardiovascular Agents; D009842:Oligopeptides; C061174:tyrosyl-prolyl-arginine; D001285:Atropine; D011433:Propranolol
Kardioprotektivnyĭ éffekt novogo otechestvennogo sinteticheskogo analoga éndogennykh opioidov pri stresse, vyzvannom total'noĭ ishemieĭ miokarda, i nekotorye ego mekhanizmy.