Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Jun;75(6):2941–2944. doi: 10.1073/pnas.75.6.2941

Beneficial and detrimental actions of histamine H1- and H2-receptor antagonists in circulatory shock

Burton M Altura *, Simon Halevy †
PMCID: PMC392682  PMID: 26917

Abstract

This study explores the use of both histamine H1- and H2-receptor antagonists in two different forms of circulatory shock and suggests that histamine may be involved in more than one way in the pathophysiology of circulatory shock. Various single doses of diphenhydramine, chlorpheniramine, promethazine, and burimamide were administered intravenously to Wistar rats subjected to hemorrhagic or bowel ischemia shock. Cumulative survival and mortality, as well as arterial blood pressures and microhematocrits, were monitored. Pretreatment of the animals with the three different H1-receptor antagonists exerted significant protection against both forms of shock. Rats pretreated with the H2-receptor antagonist, burimamide, demonstrated an exacerbated mortality after induction of shock. Animals pretreated with H1-receptor antagonists showed significantly higher mean arterial blood pressure, greater compensatory rebound of blood pressure after induction of shock, and greater responses to transfusion after hemorrhage than control, shocked animals. Similarly, rats pretreated with the H1-receptor blockers demonstrated significantly greater compensatory hemodilution which continued late in shock. In marked contrast, rats pretreated with burimamide exhibited opposite effects after hemorrhage and bowel ischemia, i.e., significant falls in blood pressure, lack of compensatory rebound and response to transfusion of shed blood, and a progressive hemoconcentration. This report clearly demonstrates beneficial actions of histamine H1-receptor antagonists and detrimental effects of H2-receptor antagonists on survival and other parameters in these forms of circulatory shock.

Keywords: hemorrhage, trauma, antihistamines, pathophysiology of shock

Full text

PDF
2941

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altura B. M., Altura B. T. Peripheral vascular actions of glucocorticoids and their relationship to protection in circulatory shock. J Pharmacol Exp Ther. 1974 Aug;190(2):300–315. [PubMed] [Google Scholar]
  2. Altura B. M., Hershey S. G., Mazzia V. D. Microcirculatory approach to vasopressor therapy in intestinal ischemic (SMA) shock. Am J Surg. 1966 Feb;111(2):186–192. doi: 10.1016/0002-9610(66)90236-4. [DOI] [PubMed] [Google Scholar]
  3. Black J. W., Duncan W. A., Durant C. J., Ganellin C. R., Parsons E. M. Definition and antagonism of histamine H 2 -receptors. Nature. 1972 Apr 21;236(5347):385–390. doi: 10.1038/236385a0. [DOI] [PubMed] [Google Scholar]
  4. Chand N., Eyre P. Classification and biological distribution of histamine receptor sub-types. Agents Actions. 1975 Oct;5(4):277–295. doi: 10.1007/BF02205232. [DOI] [PubMed] [Google Scholar]
  5. Emerson T. E., Jr Participation of endogenous vasoactive agents in the pathogenesis of endotoxin shock. Adv Exp Med Biol. 1971 Oct;23(0):25–45. doi: 10.1007/978-1-4615-9014-9_4. [DOI] [PubMed] [Google Scholar]
  6. Ercan Z. S., Türker R. K. Histamine receptors in the cat mesenteric circulation. Experientia. 1976 Jan 15;32(1):89–90. doi: 10.1007/BF01932639. [DOI] [PubMed] [Google Scholar]
  7. FINE J., FRANK H. A., FRIEDMAN E. W., GLOTZER P., JACOB S., LEVENSON S. Antiadrenergic and antihistaminic therapy in hemorrhagic shock in dog and rat. Am J Physiol. 1956 Jul;186(1):79–84. doi: 10.1152/ajplegacy.1956.186.1.79. [DOI] [PubMed] [Google Scholar]
  8. FINE J. PATTERNS OF INTESTINAL ISCHAEMIA. Lancet. 1965 Feb 6;1(7380):320–321. doi: 10.1016/s0140-6736(65)91060-3. [DOI] [PubMed] [Google Scholar]
  9. ICK J. A. BIOASSAY OF THE PROMINENT HUMORAL AGENTS INVOLVED IN ENDOTOXIN SHOCK. Am J Physiol. 1965 Jul;209:75–78. doi: 10.1152/ajplegacy.1965.209.1.75. [DOI] [PubMed] [Google Scholar]
  10. JANOFF A., NAGLER A. L., BAEZ S., ZWEIFACH B. W. Pathogenesis of experimental shock. III. A lethal factor in the blood of rabbits following occlusion of the superior mesentric artery. J Exp Med. 1961 Aug 1;114:205–216. doi: 10.1084/jem.114.2.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jakschik B. A., Marshall G. R., Kourik J. L., Needleman P. Profile of circulating vasoactive substances in hemorrhagic shock and their pharmacologic manipulation. J Clin Invest. 1974 Oct;54(4):842–852. doi: 10.1172/JCI107824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KOBOLD E. E., THAL A. P. QUANTITATION AND IDENTIFICATION OF VASOACTIVE SUBSTANCES LIBERATED DURING VARIOUS TYPES OF EXPERIMENTAL AND CLINICAL INTESTINAL ISCHEMIA. Surg Gynecol Obstet. 1963 Sep;117:315–322. [PubMed] [Google Scholar]
  13. Markley K., Horakova Z., Smallman E. T., Beaven M. A. The role of histamine in burn, tourniquet and endotoxin shock in mice. Eur J Pharmacol. 1975 Sep-Oct;33(2):255–265. doi: 10.1016/0014-2999(75)90169-7. [DOI] [PubMed] [Google Scholar]
  14. McNeill J. H., Verma S. C. Blockade by burimamide of the effects of histamine and histamine analogs on cardiac contractility, phosphorylase activation and cyclic adenosine monophosphate. J Pharmacol Exp Ther. 1974 Jan;188(1):180–188. [PubMed] [Google Scholar]
  15. Reinhardt D., Wiemann H. M., Schümann H. J. Effects of the H1-antagonist promethazine and the H2-antagonist burimamide on chronotropic, inotropic and coronary vascular responses to histamine in isolated perfused guinea-pig hearts. Agents Actions. 1976 Nov;6(6):683–688. doi: 10.1007/BF02026088. [DOI] [PubMed] [Google Scholar]
  16. Süsskand K., Siess M., Sewing K. F. Effect of histamine H2-receptor and beta-receptor blockade on histamine-, orciprenaline- and prostaglandin-stimulated frequency of the isolated guinea-pig atrium. Agents Actions. 1975 Dec;5(5):444–447. doi: 10.1007/BF01972664. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES