title: Investigation of the mineralocorticoid and hypertensinogenic activity of 18-hydroxycortisol in conscious sheep.
abstract: The increased urinary excretion of 18-hydroxycortisol (18-OHF) in patients with primary aldosteronism has raised the possibility that 18-OHF is involved in the maintenance and/or pathogenesis of the associated hypertension. This study has investigated the mineralocorticoid, glucocorticoid, and hypertensinogenic activities of 18-OHF in the conscious sheep. Infusion of 18-OHF (400 micrograms/h i.v. 5 days; n = 5) alone had no effect on blood pressure or on fluid and electrolyte balance. Infusion of a combination of five adrenal steroids (aldosterone 3 micrograms/h, cortisol 5 mg/h, corticosterone 0.5 mg/h, 11-deoxycortisol 1 mg/h and deoxycorticosterone 25 micrograms/h, i.v. 5 days; n = 5) increased blood pressure by 14 +/- 1 mmHg (p < .001), but when 18-OHF was infused together with the five adrenal steroids, no additional increase in blood pressure was observed. In another group of sheep (n = 4) 18-OHF was infused at a range of doses (5, 50, 100, 200, 500, and 1000 micrograms/h i.v.), each for 2 h, into sodium-replete and sodium-deplete, adrenalectomized sheep. 18-OHF had no effect on the urinary sodium or potassium excretion or on the salivary Na/K ratio in either group as compared with vehicle infusion. To examine the renal effects of 18-OHF, a range of doses of 18-OHF (5, 50, 100, 200, 500, and 1000 micrograms/h) were infused directly into the renal artery of conscious sheep (n = 4). 18-OHF did not affect the renal blood flow nor the urinary sodium or potassium excretion compared with vehicle infusion. In summary, we could not demonstrate any mineralocorticoid, glucocorticoid, or hypertensiongenic effects of 18-OHF in conscious sheep at a dose of 400 micrograms/h. Thus, a cautious approach to interpreting the role that 18-OHF plays in the clinical manifestations of primary aldosteronism, is necessary.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: De Matteo
authors.forename: C N
authors.initials: CN
authors.lastname: May
authors.forename: J P
authors.initials: JP
authors.lastname: Coghlan
authors.forename: T
authors.initials: T
authors.lastname: Kurosawa
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
authors.forename: H
authors.initials: H
authors.lastname: Chiba
authors.forename: J G
authors.initials: JG
authors.lastname: McDougall
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012463:Saliva / Q000187:drug effects; D012756:Sheep; D012964:Sodium / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D012964:Sodium; D011188:Potassium; C033689:18-hydroxycortisol; D006854:Hydrocortisone