THROMBIN DOES NOT ALTER VASCULAR HYPOREACTIVITY IN MODELS OF ENDOTOXIN-INDUCED SEPTIC SHOCK IN RATS

1. Hypotension and vascular hyporesponsiveness to vasoconstrictors are observed during endotoxic shock, and are associated with increased pr oduction of nitric oxide in the vascular wall, Disseminated intravascu lar coagulation is another feature of septicaemia, We hypothesized tha t thrombin generated during disseminated intravascular coagulation mig ht modulate the changes in vascular tone induced by endotoxin. 2. Incu bation of rat aortic rings for 4 h with alpha-thrombin (0.003-3.0 NIH units/ml) did not change their reactivity to noradrenaline, Incubation for 4 h with lipopolysaccharide increased the EC(50) for noradrenalin e, whereas co-incubation of thrombin (0.5 NIH units/ml) with lipopolys accharide did not alter this hyporeactivity to noradrenaline. 3. In vi vo in rats, lipopolysaccharide caused early (1 h) and late (4-6 h) hyp oreactivity to noradrenaline, In rats infused with lipopolysaccharide and heparin (1 U min(-1) kg(-1), 0.4 ml/h or hirudin (2.2 mg ml(-1) kg (-1), 0.8 ml/h), vasopressor responses to noradrenaline were not diffe rent from those after infusion of lipopolysaccharide alone, Aortic rin gs taken from rats receiving both anticoagulant treatment and lipopoly saccharide had the same sensitivity to noradrenaline as those obtained from rats receiving lipopolysaccharide alone. 4. Our results suggest that, in vivo, disseminated intravascular coagulation does not modify the early and late effects of lipopolysaccharide on arterial pressure and that, in vitro, thrombin neither induces hyporeactivity to noradre naline nor modifies lipopolysaccharide-induced hyporeactivity, We prop ose that thrombin generated during disseminated intravascular coagulat ion in rats does not play a major role in the alterations of vascular tone observed during endotoxic shock.