Co-Authors:
Feuerstein, G., Neurobiology Research Unit, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
Lux, W.E., Jr., Neurobiology Research Unit, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
Ezra, D., Section on Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
Hayes, E.C., Merck Institute for Therapeutic Research Railway, NJ, United States
Snyder, F., Oak Ridge Associated Universities, Oak Ridge, TN, United States
Faden, A.I., Neurobiology Research Unit, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
Abstract:
Platelet-activating factor (PAF) and leukotrienes, newly described classes of vasoactive lipids, may play a role in anaphylaxis. It has recently been suggested that the vasoconstrictor effects of PAF in isolated rat lung are related to release of leukotrienes C4 and D4. Thyrotropin-releasing hormone (TRH), a tripeptide, has potent antihypotensive activity in experimental shock, including that resulting from either leukotriene D4 administration or antigen-induced anaphylaxis. We utilized an unanesthetized guinea pig model to study the relationships among PAF, leukotrienes, and TRH and their potential interactions on the cardiovascular system. PAF (1 nmol/600 g body weight i.v.) produced profound hypotension which was completely blocked by TRH (2 mg/kg i.v.). Nafazatrom or FPL 55712, a presumed receptor antagonist of leukotrienes, was ineffective, whereas U-60257, a leukotriene synthesis inhibitor, displayed incomplete blockade. Moreover, leukotriene-like immunoreactivity in plasma did not increase following PAF administration. Thus, hypotension produced by PAF does not appear to result secondarily from release of cysteinyl leukotrienes. Moreover, the ability of TRH to block the hypotensive effects of PAF may partially account for its beneficial effects in experimental anaphylaxis and provides further rationale for the therapeutic evaluation of this peptide in anaphylactic shock. © 1985 Raven Press, New York.