Hypotension produced by platelet-activating factor is reversed by thyrotropin-releasing hormone

Platelet-activating factor (PAF), a vasoactive phospholipid implicated in anaphylactic reactions, causes severe hypotension in experimental animals that is highly resistant to pharmacological therapy. In the present studies, we showed that PAF (1 nmol/600 g body weight, IV) produced profound hypotension in unanesthetized guinea pigs that was promptly and completely reversed by thyrotropin-releasing hormone (TRH) (2 mg/kg, IV) or by the synthetic TRH analog MK771 (2 mg/kg, IV). TRH also reversed this hypotension when administered intracerebroventricularly (ICV) at a dose (0.02 mg/kg) that was systemically ineffective. The opiate receptor antagonist naloxone (5 mg/kg) was less effective than TRH in reversing the cardiovascular consequences of PAF administration. These data suggest that TRH reverses PAF-induced shock through central receptor-mediated mechanisms. This therapeutic action of TRH may partially account for the beneficial cardiovascular effects of this peptide in anaphylactic shock.