Transcerebral net exchange of vasoactive peptides and catecholamines during lipopolysaccharide-induced systemic inflammation in healthy humans

The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a four-hour intravenous LPS infusion (0.3 ng kg^-1) induces any changes in the transcerebral net exchange of the vasoactive peptides endothelin-1 (ET-1) and calcitonin-gene related peptide (CGRP) and catecholamines in human volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique, and paired arterial-to-jugular venous blood samples were obtained for estimating the transcerebral exchange of ET-1, CGRP and catecholamines by the Fick principle in twelve volunteers before and after LPS. The cerebrovascular release of ET-1 was enhanced, while the transcerebral net exchange of CGRP and catecholamines was unaffected. Our findings thus point towards locally produced ET-1 within the cerebrovasculature as a contributor to cerebral vasoconstriction after LPS.