title: Cortisol inhibits cholinergic vasodilation in the human forearm.
abstract: Exogenous cortisol raises blood pressure (BP) in humans and there is accumulating evidence of abnormalities of glucocorticoid activity in essential hypertension. In this study we tested the hypothesis that exogenous cortisol attenuates the cholinergic dilator response in the forearm circulation. Fourteen healthy normotensive men were studied. Using bilateral forearm venous plethysmography, we examined forearm blood flow responses to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) pre- and post-NG-monomethyl-L-arginine (LNMMA) after 2 or 5 days of oral cortisol or placebo in a randomized, double-blind crossover study. Exogenous cortisol increased supine systolic (P < .05) and standing systolic (P < .05) BP and produced expected metabolic changes and suppressed serum cortisol concentration (P < .001). Baseline forearm blood flow did not differ between placebo and cortisol treatments at 2 or 5 days. Cholinergic vasodilatation was impaired after cortisol administration, reaching statistical significance at 5 days (P < .05). Cortisol did not affect responses to SNP. NG-monomethyl-L-arginine inhibited cholinergic vasodilatation in placebo-treated groups but had no additional effect in the presence of cortisol. These results support our hypothesis and suggest that the mechanism of impaired cholinergic dilatation in glucocorticoid-treated subjects involves abnormalities of the endothelial nitric oxide system.
authors.affiliation: Department of Medicine, St George Hospital, University of New South Wales, Kogarah, Australia. g.mangos@unsw.edu.au
authors.forename: G J
authors.initials: GJ
authors.lastname: Mangos
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: J J
authors.initials: JJ
authors.lastname: Kelly
authors.forename: J A
authors.initials: JA
authors.lastname: Lawson
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
authors.forename: J A
authors.initials: JA
authors.lastname: Whitworth
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone