Thyrotropin-Releasing Hormone Blocks the Hypotensive Effects of Platelet-Activating Factor in the Unanesthetized Guinea Pig

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Abstract
Platelet-activating factor (PAF) and leukotrienes [LT], newly described classes of vasoactive lipids may play a role in anaphylaxis. The vasoconstrictor effects of PAF in isolated rat lung are related to release of LT C4 and D4. TRH, a tripeptide, has potent antihypotensive activity in experimental shock, including that resulting from either LT D4 administration or antigen-induced anaphylaxis. An unanesthetized guinea pig model was used to study the relationships among PAF, LT 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 LT, was ineffective, i.e., U-60257, a LT synthesis inhibitor, displayed incomplete blockade. LT-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 LT. 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.