Accession Number : ADA189506

Title :   The Role of Endorphins in the Pathophysiology of Hemorrhagic and Endotoxic Shock in the Subhuman Primate.

Descriptive Note : Final rept. 1 Jun 80-13 Mar 85,

Corporate Author : IOWA UNIV IOWA CITY COLL OF MEDICINE

Personal Author(s) : Gurll, Nelson J ; Reynolds, David G ; Vargish, Thomas ; Gisolfi, Carl V

PDF Url : ADA189506

Report Date : 15 Mar 1985

Pagination or Media Count : 66

Abstract : In order to investigate the pathophysiological role of endogenous morphine-like substances (endorphins for short) in shock, we studied cynomolgus monkeys and dogs subjected to hemorrhagic or endotoxic shock. Blockade of opiate receptors with naloxone improved cardiovascular function (mean arterial pressure, cardiac output, and myocardial contractility) in both species and both models but requires correction of acidosis and hypothermia. Shock is associated with elevations in plasma levels of Beta-endorphin and Beta-lipotropin. Using different sites of injection and various pharmacological and anatomical ablations, we have shown that naloxone's beneficial effects in hemorrhagic shock are due to potentiation of the effects of released catecholamines on cardiac opiate receptors. The myocardial depression found in shock is due to an endorphin-induced attenuation of catecholamine effects on the heart. We believe this is mediated by interaction with cardiac receptors and is expressed via G-protein activation of adenylate cyclase and cyclic-AMP. This hypothesis needs to be tested by biochemical determination of these substances, and our observations need to be extended to endotoxic shock. Nevertheless, naloxone and other antiendorphin substances may be important in the treatment of shock by reversing one of the important pathophysiological mechanisms of cardiovascular depression. Keywords: Thyrotropin releasing hormone.

Descriptors :   *ENDOTOXIC SHOCK, *HEMORRHAGIC SHOCK, *PATHOPHYSIOLOGY, *PITUITARY HORMONES, *PHARMACOLOGICAL ANTAGONISTS, ACIDOSIS, ADENYL CYCLASE, BIOCHEMISTRY, BLOOD PRESSURE, CARDIOVASCULAR SYSTEM, CATECHOLAMINES, CONTRACTION, CORRECTIONS, DETERMINATION, DOGS, HEART, HORMONES, HUMANS, HYPOTHERMIA, HYPOTHESES, INJECTION, MEAN, MONKEYS, MYOCARDIUM, OUTPUT, PATHOLOGY, PHYSIOLOGY, PRIMATES, RELEASE, SITES, THYROTROPIN, PEPTIDES

Subject Categories : Medicine and Medical Research
      Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE