Effect of synthetic corticosteroids on vascular reactivity in the human forearm.
Exogenous cortisol raises blood pressure (BP) and suppresses acetylcholine (ACh)-induced vasodilatation in healthy male volunteers. This study tests the hypothesis that the activation of either classical type I or II corticosteroid receptors by synthetic corticosteroids induces endothelial dysfunction. In two separate studies, dexamethasone or fludrocortisone was administered to healthy male subjects over five days. BP, metabolic parameters, and forearm blood flow (FBF) responses to intra-arterial ACh and nitroprusside (SNP) were measured on day 5 of treatment. Fludrocortisone (800 microg/day) and dexamethasone (3 mg/day) increased BP from control measurements, but not when compared with placebo. Metabolic effects of the steroids were consistent with their known actions. Endothelium-dependent vasodilatation was enhanced by fludrocortisone, most obviously in the presence of nitric oxide (NO) synthase inhibition with NG-mono-methyl-L-arginine (LNMMA). Dexamethasone did not suppress endothelium dependent or independent vasodilatation. Non-NO-mediated endothelium-dependent vasodilatation was increased by systemic mineralocorticoid excess but unaffected by glucocorticoid excess. These results do not support the notion that cortisol-induced vascular effects are mediated through classical corticosteroid receptors.
Mangos
George J
GJ
Department of Medicine and Renal Medicine, St. George Hospital, University of New South Wales, Kogarah, Australia.
Walker
Brian R
BR
Williamson
Paula A
PA
Whitworth
Judith A
JA
Kelly
John J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005438:Fludrocortisone / Q000008:administration & dosage*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011987:Receptors, Steroid / Q000187:drug effects; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000305:Adrenal Cortex Hormones; D004791:Enzyme Inhibitors; D011987:Receptors, Steroid; D019323:omega-N-Methylarginine; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D005438:Fludrocortisone