INVOLVEMENT OF BRADYKININ AND NITRIC-OXIDE IN THE EARLY HEMODYNAMIC-EFFECTS OF LIPOPOLYSACCHARIDE IN RATS

The involvement of bradykinin and nitric oxide (NO) in the early (with in 1 h) hemodynamic effects of bacterial lipopolysaccharide (LPS) were investigated in anaesthetised rats. Infusion of rats with LPS (14 mg/ kg/h) produced a transient hypotension (nadir at 20 min) and reduced p resser responses to noradrenaline (NA, .1-1 mu g/kg, intravenously (i. v.)). Pretreatment of rats with N-G-nitro-L-arginine methylester (L-NA ME, 1 mg/kg, i.v.) produced an hypertension which counteracted but did not abolish the hypotension induced by LPS, although it entirely prev ented LPS-induced hyporeactivity to NA. In control rats, the bradykini n B2 receptors antagonist HOE 140 (10 nmol/kg, i.v.) produced a transi ent hypotension, but it did not modify the reactivity to NA. In rats p retreated with HOE 140, subsequently infused with LPS, the drop in blo od pressure and its time course after the onset of LPS infusion were n ot different from those elicited by HOE 140 or LPS separately. In addi tion, HOE 140 partially prevented the onset of hyporesponsiveness to N A induced by LPS. These results support the view that both bradykinin and NO are involved in the early hyporesponsiveness to NA. They sugges t that other mechanisms than NO release are involved in the early hypo tensive effects of LPS.