title: Acute intrarenal administration of cortisol has no effect on renal blood flow in hypertensive individuals.
abstract: BACKGROUND
  Cortisol is known to increase blood pressure. One possible mechanism is the reported increase in renal vascular resistance (RVR). It is unknown whether this is due to a direct effect of cortisol on the kidneys.
  
  
  OBJECTIVE
  To study the effect of infusion of cortisol directly into the renal artery on renal blood flow (RBF) and on renal 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-mediated conversion of cortisol to cortisone in patients with primary hypertension.
  
  
  METHODS
  Twenty-seven patients with primary hypertension participated in this study. Fifteen received placebo and 12 received glycyrrhetinic acid (GRA; 500 mg) orally 2.5 h before the study. After a 10 min infusion of 5% glucose, cortisol was infused in stepwise increasing doses (0.625, 1.25 and 2.5 microg/kg per min), for 10 min each dose. At the end of each infusion step, RBF was measured using the xenon-133 washout technique. Plasma samples from the femoral artery and renal vein were taken for measurement of cortisol and cortisone. Urine was collected for measurement of steroid concentrations for 6 h on the day before the infusion and for 6 h after the infusion.
  
  
  RESULTS
  After placebo or GRA, cortisol infusion did not change RVR, RBF or blood pressure. RVR values were 0.72 (0.45-0.89) mmHg/ml per min per 100 ml tissue [median (first and third quartiles)] and 0.71 (0.64-0.91) mmHg/ml per min per 100 ml tissue during infusion of 5% glucose and infusion of the highest dose of cortisol, respectively ( P= NS). Cortisol infusion increased the venous-arterial difference in plasma cortisone concentration across the kidney from 76 (40-115) nmol/l to 138 (100-186) nmol/l (P< 0.05) and increased the cortisol : cortisone ratios in the renal vein and in urine (both P< 0.05). As compared with placebo, administration of GRA increased the cortisol : cortisone ratios in peripheral and renal veins and in the urine.
  
  
  CONCLUSIONS
  Acute infusion of cortisol in high doses directly into the renal artery in patients with primary hypertension did not affect RBF or RVR. Infusion of cortisol resulted in increased cortisol-cortisone conversion by renal 11beta-HSD2, but the concurrent increase in renal and urinary cortisol : cortisone ratio suggests a relative insufficiency of renal 11beta-HSD2 activity as a result of enzyme saturation. This may enhance mineralocorticoid receptor stimulation by cortisol.
authors.affiliation: Division of General Internal Medicine, Division of Endocrinology, Department of Medicine, University Medical Center, Nijmegen, The Netherlands.
authors.forename: Stan H M
authors.initials: SH
authors.lastname: van Uum
authors.forename: Alphons J H M
authors.initials: AJ
authors.lastname: Houben
authors.forename: Ad R M M
authors.initials: AR
authors.lastname: Hermus
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.forename: C G J
authors.initials: CG
authors.lastname: Sweep
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003348:Cortisone / Q000097:blood / Q000652:urine; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D006973:Hypertension / Q000139:chemically induced*; D008875:Middle Aged; D012077:Renal Artery; D012079:Renal Circulation / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D006034:Glycyrrhetinic Acid; D003348:Cortisone; D006854:Hydrocortisone