Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rats: effects of pre- or post-treatment with glibenclamide

1 To determine the putative contribution of K-ATP-channels to the haemodyna mic sequelae of endotoxaemia. three experiments were carried out in differe nt groups of conscious, chronically-instrumented, unrestrained, male Long E vans rats. 2 Tn the first experiment, pretreatment with the K-ATP-channel antagonist, glibenclamide, abolished the initial hypotension, but not the renal vasodil atation caused by LPS infusion. Subsequently, however, in the presence of g libenclamide and LPS there was a significant increase in mean arterial bloo d pressure, and a bradycardia, in contrast to the fall in mean arterial blo od pressure and the tachycardia seen in the presence of vehicle and LPS. Th e presser and bradycardic changes in the presence of glibenclamide and LPS were accompanied by significant reductions in hindquarters flow and vascula r conductance, and these were significantly greater than those seen in the presence of vehicle and LPS, or glibenclamide and saline. 3 Administration of glibenclamide 6 h after the onset of saline and LPS inf usion, or 6 h after the onset of saline and LPS infusion in the presence of the AT(1)-receptor antagonist, losartan, and the ETA-, ETB- receptor antag onist, SE 209670, in the absence or presence of dexamethasone, caused a sig nificant increase in mean arterial blood pressure and reductions in renal, mesenteric and hindquarters conductances, although the latter was the only vascular bed in which there was a reduction in flow. 4 The results are consistent with a contribution from K-ATP-channels to the vasodilatation caused by LPS, particularly in the hindquarters vascular be d.