title: Short-term cortisol infusion in the brachial artery, with and without inhibiting 11 beta-hydroxysteroid dehydrogenase, does not alter forearm vascular resistance in normotensive and hypertensive subjects.
abstract: BACKGROUND
  Vascular tone is increased in primary hypertension, and glucocorticoids affect vascular tone. Local cortisol availability is modulated by activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). As this activity may be decreased in patients with primary hypertension, vascular sensitivity to cortisol may be increased in these patients. We studied the acute effect of cortisol on forearm vascular resistance (FVR) by infusing cortisol directly into the brachial artery, both with and without inhibition of 11 beta-HSD, in normotensive and hypertensive subjects.
  
  
  METHODS
  Twenty normotensive volunteers and 20 patients with primary hypertension participated in the study. After a 10-min infusion of vehicle (glucose 5%), cortisol was infused into the brachial artery in three stepwise increasing doses (3.5, 10.5 and 35 microg per 100 mL of forearm volume), each for 10 min. Next, the participants received placebo or 500 mg glycyrrhetinic acid (GA) orally, and 150 min later the same infusion schedule was repeated. Forearm vascular resistance was measured during the last 5 min of the infused vehicle and of each dose. Arterial and forearm venous plasma samples for measurement of cortisol and cortisone were taken at the end of the infusions of glucose 5% and the highest cortisol dose.
  
  
  RESULTS
  In both normotensive and hypertensive subjects, neither the infusion of cortisol nor the administration of GA changed FVR. Also 2 h after the cortisol infusion there remained no change in FVR in both the normotensive and hypertensive groups who received placebo. Following the infusion of the highest cortisol dose, total plasma cortisone levels in the venous plasma were decreased compared with levels in the arterial plasma (36 +/- 3 and 49 +/- 4 nmol L-1, respectively, P < 0.05). The protein-bound venous cortisone was 37.1 +/- 4.8 nmol L-1 during the vehicle compared with 23.9 +/- 3.7 nmol L-1 during the cortisol infusion (P < 0.01), whereas the free cortisone level was not altered by the cortisol infusion.
  
  
  CONCLUSIONS
  In both normotensive and hypertensive subjects, high-dose cortisol infusion both with and without 11 beta-HSD inhibition did not change FVR either immediately or after 2 h. We could not demonstrate in vivo 11 beta-HSD activity in the forearm vascular tissues. When binding of cortisone to CBG is changed, e.g. during cortisol infusion, arterio-venous changes in cortisone cannot reliably be used to assess (alterations in) local 11 beta-HSD activity.
authors.affiliation: Department of Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: S H M
authors.initials: SH
authors.lastname: van Uum
authors.forename: A R M M
authors.initials: AR
authors.lastname: Hermus
authors.forename: C G J
authors.initials: CG
authors.lastname: Sweep
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: H A
authors.initials: HA
authors.lastname: Ross
authors.forename: P W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: J W M
authors.initials: JW
authors.lastname: Lenders
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D001916:Brachial Artery; D016022:Case-Control Studies; D003348:Cortisone / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006034:Glycyrrhetinic Acid; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D003348:Cortisone; D006854:Hydrocortisone