Most cardiometabolic diseases are characterized by increased muscle sympathetic nerve
activity (MSNA) during rest and exercise which contributes to poor health outcomes. In
healthy humans during muscle contraction, there is a blunting of skeletal muscle vascular
responsiveness to increases in MSNA. However, the exact mechanisms involved are unknown
although, best evidence suggests that the mechanism is endothelium derived, but nitric oxide
(NO) and prostaglandin (PG) independent. Endothelium-derived hyperpolarizing factor (EDHF) is
a NO and PG independent vasodilator in both cerebral and skeletal muscle circulations,
however, it is unknown if EDHF contributes to vascular responsiveness during elevated MSNA.
The application of lower body negative pressure (LBNP) is a safe and non-invasive
manipulation that can be used to increase MSNA causing vasoconstriction in humans. Therefore,
the purpose of this experiment is to determine if acute inhibition of EDHF alters central and
peripheral vascular responses to LBNP at rest and during dynamic exercise. Thereby, providing
evidence by which EDHF contributes to vascular control in healthy humans and identify it's
potential as a therapeutic target for cardiometabolic diseases that are characterized by
elevated MSNA