Leukotriene D4-induced hypotension is reversed by thyrotropin-releasing hormone

Injection of leukotriene D4 (LTD4, 20 micrograms/kg, i.a.) to conscious spontaneous hypertensive (SHR) rats produces a short-lasting pressor and tachycardic response followed by prolonged hypotension and bradycardia. Plasma norepinephrine and epinephrine were elevated at the peak pressor/tachycardic phase as well as at the hypotensive phase. Injection of thyrotropin-releasing hormone (TRH, 2 or 5 mg/kg) at the peak of the LTD4-induced hypotension resulted in prompt reversal of the hypotension and bradycardia in a dose-related manner. Naloxone (5 mg/kg) had no effect on blood pressure and heart rate of LTD4-treated SHR rats. Pretreatment with TRH (5 mg/kg) did not prevent the depressor effect of LTD4, but attenuated the bradycardic effect of this leukotriene. In addition, TRH had no effect on LTD4-induced hypotension in the pithed SHR rat. These results suggest that TRH might exert beneficial effects in hypotensive states mediated by leukotrienes or other mediators of anaphylactic reactions.