enkephalin--leucine-2-alanine and Hemorrhage

The experiments have been performed on 93 male rats, weighing 200-250 g. In acute blood loss various arterial pressure (AP) changes have been demonstrated--the marked hypertension is being changed by gradual AP increase. The injection of m-receptors' agonist DAGO prevents systolic and diastolic AP increase, agonist DADL prevents diastolic AP increase in acute momentary blood loss. In gradual blood loss DAGO (more than DADL) slows down both the decrease and the subsequent AP increase in rats. DAGO is determined to decrease, and DADL--to increase the minute blood volume. The mechanisms of opioids' action and their significance in pathogenesis of hemodynamic disturbances in shock are being discussed.

Topics: Acute Disease; Animals; Drug Evaluation, Preclinical; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Hemodynamics; Hemorrhage; Male; Rats; Rats, Inbred Strains; Receptors, Opioid; Shock, Hemorrhagic; Time Factors

The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.

Topics: Animals; Blood Pressure; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Hemorrhage; Injections, Intravenous; Kallikreins; Kinins; Male; Naloxone; Rats; Rats, Inbred Strains; Shock, Hemorrhagic

The role and possible clinical use of regulatory peptides, a new type of regulatory substances, is discussed. Special attention is paid to the opioid peptides and their analogues. The new drug dalargin has been developed on the basis of the endogenous opioid peptide leucine-encephalin. Its action has been studied using experimental models. It has been established that the optimal dose (10 micrograms/kg) of dalargin is effective in preventing ulceration in the cystamine duodenal ulcer rat model and the development of stomach erosive lesions in immobilization stress, reducing the degree of liver degeneration in CCl4 poisoning, etc. With an increase of the dose of dalargin the effect "escapes". Dalargin is primarily bound by delta-receptors, it produces no analgetic effect and does not enter the brain. Dalargin exhibits a pronounced cytoprotective and regeneratory action and may take an important place in treating the internal organ diseases.

Topics: Animals; Carbon Tetrachloride Poisoning; Cells, Cultured; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Hemorrhage; Humans; Lymphocytes; Mice; Necrosis; Pancreas; Rats; Receptors, Opioid; Stomach Ulcer