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 haemodynamic sequelae of endotoxaemia, three experiments were carried out in different groups of conscious, chronically-instrumented, unrestrained, male Long Evans rats. 2. In the first experiment, pretreatment with the K(ATP)-channel antagonist, glibenclamide, abolished the initial hypotension, but not the renal vasodilatation caused by LPS infusion. Subsequently, however, in the presence of glibenclamide and LPS there was a significant increase in mean arterial blood pressure, and a bradycardia, in contrast to the fall in mean arterial blood pressure and the tachycardia seen in the presence of vehicle and LPS. The pressor and bradycardic changes in the presence of glibenclamide and LPS were accompanied by significant reductions in hindquarters flow and vascular 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 infusion, or 6 h after the onset of saline and LPS infusion in the presence of the AT(1)-receptor antagonist, losartan, and the ET(A)-, ET(B)- receptor antagonist, SB 209670, in the absence or presence of dexamethasone, caused a significant 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 bed.