Effect of thyrotropin-releasing hormone on lipoxygenase-induced hypotension in the unanesthetized Guinea pig.

Soybean lipoxygenase, an enzyme which catalyzes the formation of the vasoactive lipid 15-hydroperoxy eicosatetraenoic acid (15-HPETE) from arachidonic acid, was administered to unanesthetized guinea pigs previously prepared with indwelling vascular cannulae for continuous cardiovascular monitoring. Administration of this enzyme (150 mg/kg IV) resulted in profound hypotension in this model, but no cardiovascular change was observed after administration of equal weight or equimolar amounts of another protein (ovalbumin). The lipoxygenase-induced hypotension, moreover, was promptly reversed by the peptide thyrotropin-releasing hormone (TRH) (2 mg/kg IV) but not by the opiate receptor antagonist naloxone (2 mg/kg IV). This TRH-naloxone dissociation was comparable to that previously observed in hypotension produced by leukotriene D4 (LTD4), platelet-activating factor (PAF), or antigen-induced anaphylaxis in the same species. Thus, although its properties as a "physiologic" opiate antagonist led to the early trials of TRH in endotoxic, hypovolemic and spinal shock, it is now apparent that TRH reverses several other forms of experimental shock, including that caused by lipoxygenase, through non-endorphin-related mechanism.