In vivo administration of LPS reduces dexmedetomidine-induced contraction in isolated rat aortae

Abstract

The vascular effects of dexmedetomidine during sepsis are largely unknown. The present experiments were designed to determine ex vivo responses to dexmedetomidine in arteries of animals after short- or long-term exposure to lipopolysaccharide (LPS). Eight to ten weeks old male SD rats received different doses of LPS or normal saline in vivo two or 72 hours prior to sacrifice. Arterial blood pressure, heart rate and plasma cytokine levels were measured before isolating their aortae. Rings, with or without endothelium, were suspended in organ chambers, for isometric tension recording. In the absence or presence of pharmacological inhibitors [ L-NAME, indomethacin, TRAM-34, UCL1684 and iberiotoxin ]. LPS injections increased the plasma levels of TNF-á and IL-6 and reduced arterial blood pressure. They dose-dependently attenuated dexmedetomidine-induced contractions whether given two or 72 hours prior to sacrifice. However, contractions were increased in preparations without endothelium, and to a lesser extent in rings with endothelium after 72 hours. In the presence of TRAM -34, but not UCL1684, dexmedetomidine-induced contractions were enhanced on rings with endothelium, while they were reduced by iberiotoxin. The present data indicate that in vivo exposure to LPS differentially attenuates the contractile responses to dexmedetomidine, an action which may involve, BKCA.