Acute effects of glucocorticoids on endothelial fibrinolytic and vasodilator function in humans.
Acute coronary events occur most commonly in the morning, when circadian variations dictate that endogenous fibrinolytic activity is low and cortisol levels are high. We hypothesized that glucocorticoids would impair the acute fibrinolytic capacity of the endothelium because chronic glucocorticoid excess is associated with a prothrombotic state and endothelial vasomotor dysfunction. Twelve healthy subjects attended on 3 occasions and received oral metyrapone followed by intravenous saline or low-dose or high-dose hydrocortisone. Forearm blood flow and fibrinolytic indices were measured using venous occlusion plethysmography during intrabrachial bradykinin, acetylcholine, and sodium nitroprusside infusion. Hydrocortisone infusion had no effect on systemic concentrations of plasminogen activator inhibitor type 1 (PAI-1) or tissue plasminogen activator (t-PA; P = 0.10 and 0.95, respectively). Bradykinin caused a dose-dependent increase in plasma t-PA concentrations (P < 0.0001) that was unaffected by systemic hydrocortisone administration. Intrabrachial infusions of bradykinin, acetylcholine, and sodium nitroprusside all caused dose-dependent increases in forearm blood flow (P < 0.05) that were unaltered by hydrocortisone infusions.Short-term variations in plasma cortisol concentrations within the physiological range do not affect endothelial fibrinolytic or vasomotor function in healthy volunteers. These findings suggest that glucocorticoids do not exert acute effects on endothelial function in vivo in humans.
Dover
Anna R
AR
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK. anna.dover@ed.ac.uk
Hadoke
Patrick W F
PW
Walker
Brian R
BR
Newby
David E
DE
D000109:Acetylcholine; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008875:Middle Aged; D009599:Nitroprusside; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D009599:Nitroprusside; D010959:Tissue Plasminogen Activator; D000109:Acetylcholine; D001920:Bradykinin; D006854:Hydrocortisone; D008797:Metyrapone