TY - JOUR

T1 - Transcerebral net exchange of vasoactive peptides and catecholamines during lipopolysaccharide-induced systemic inflammation in healthy humans

AU - Berg, Ronan M G

AU - Taudorf, Sarah

AU - Bailey, Damian M

AU - Dahl, Rasmus H

AU - Lundby, Carsten

AU - Møller, Kirsten

PY - 2018

Y1 - 2018

N2 - The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a 4-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 12 volunteers before and after LPS infusion. The cerebrovascular release of ET-1 was enhanced, whereas 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 infusion.

AB - The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a 4-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 12 volunteers before and after LPS infusion. The cerebrovascular release of ET-1 was enhanced, whereas 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 infusion.

KW - Adult

KW - Brain/blood supply

KW - Calcitonin Gene-Related Peptide/metabolism

KW - Catecholamines/metabolism

KW - Endothelin-1/metabolism

KW - Healthy Volunteers

KW - Humans

KW - Lipopolysaccharides/pharmacology

KW - Male

KW - Systemic Inflammatory Response Syndrome/metabolism

KW - Vasoconstriction/drug effects

U2 - 10.1139/cjpp-2017-0266

DO - 10.1139/cjpp-2017-0266

M3 - Journal article

C2 - 28898586

VL - 96

SP - 313

EP - 316

JO - Canadian Journal of Physiology and Pharmacology

JF - Canadian Journal of Physiology and Pharmacology

SN - 0008-4212

IS - 3

ER -