title: Urinary cortisol is inversely associated with capillary recruitment in women: a potential explanation for the cortisol-blood pressure relationship.
abstract: The relationships of cortisol with elevated blood pressure and insulin resistance are likely to be the result of a complex interplay of different mechanisms. We hypothesize that cortisol is associated with impaired microvascular function and that this contributes to cortisol-associated high blood pressure and insulin resistance. We examined 24 h urinary free cortisol excretion in 56 healthy adults (26 women). Blood pressure was assessed by 24 h ambulatory measurements. Insulin sensitivity was determined using the hyperinsulinaemic euglycaemic clamp technique. Skin capillary recruitment after arterial occlusion was visualized with videomicroscopy and endothelium-(in)dependent vasodilation was evaluated with iontophoresis of acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry. Men were characterized by higher urinary cortisol excretion [median (interquartile range), 162 (130-194) compared with 118 (99-156) nmol/24 h, P<0.05]. In women, but not in men, urinary cortisol excretion was associated with impaired capillary recruitment (r=-0.66, P<0.001), higher systolic blood pressure (r=0.64, P<0.001) and lower insulin sensitivity (r=-0.43, P<0.05). Urinary cortisol excretion was not associated with endothelium-(in)dependent vasodilation in men or women. Regression analysis demonstrated that capillary recruitment statistically explained 37% of the association between urinary cortisol and blood pressure in women. Capillary recruitment did not explain part of the association between urinary cortisol and insulin sensitivity. In conclusion, urinary cortisol excretion is inversely associated with capillary recruitment in women, but not in men, and capillary recruitment explains part of the cortisol-blood pressure relationship. These data suggest that, in women, impairment of capillary function mediates some of the adverse effects of cortisol and thus may provide a target to prevent such adverse effects.
authors.affiliation: Department of Internal Medicine, Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, De Boelelaan, Amsterdam, The Netherlands. rt.dejongh@vumc.nl
authors.forename: Renate T
authors.initials: RT
authors.lastname: de Jongh
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ijzerman
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: Mirjam M
authors.initials: MM
authors.lastname: van Weissenbruch
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Voordouw
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000502:physiology*; D018660:Blood Pressure Monitoring, Ambulatory; D002196:Capillaries; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D007333:Insulin Resistance; D007478:Iontophoresis; D008026:Ligation; D008297:Male; D018715:Microscopy, Video; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012044:Regression Analysis; D012737:Sex Factors; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D006854:Hydrocortisone