title: Aldosterone acts on the kidney, not the brain, to cause mineralocorticoid hypertension in sheep.
abstract: OBJECTIVE
  To determine the extent to which mineralocortioid hypertension depends on a direct action of aldosterone on the kidney or on the brain.
  
  
  METHODS
  Studies were performed in conscious sheep that were previously uninephrectomized, implanted with silastic cannulae in the renal artery of the remaining kidney, and had guide tubes implanted over the lateral cerebral ventricles. The effect of aldosterone, infused either intrarenally (i.r.; 2 microg/h) or intravenously (i.v.; 2 and 10 microg/h) for 10 days (n = 5), on arterial pressure and fluid and electrolyte balance was determined. The i.r. (2 microg/h) and i.v. (10 microg/h) doses were calculated to give similar intrarenal concentrations of aldosterone. In a further study, the effect of intracerebroventricular (i.c.v.) infusion of aldosterone (2 microg/h for 21 days) on arterial pressure was examined (n = 5).
  
  
  RESULTS
  Infusion of aldosterone caused a progressive increase in mean arterial pressure from 83 +/- 3 mmHg to a maximum of 100 +/- 4 mmHg (P < 0.001) with 2 microg/h i.r. and from 84 +/- 3 mmHg to a maximum of 104 +/- 4 mmHg (P < 0.001) with 10 microg/h i.v., both by day 7. With both infusions there were similar increases in plasma [Na+] and decreases in plasma [K+] and total protein concentration (P < 0.05) between days 3 and 5; these were maintained throughout the infusion. There were no significant changes with i.v. aldosterone (2 microg/h). Long-term i.c.v. infusion of aldosterone (2 microg/h for 21 days) caused no change in arterial pressure.
  
  
  CONCLUSIONS
  In conscious sheep the hypertensive response to aldosterone resulted from an action on the kidney, with no evidence for a direct action on the brain.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Leopoldo A Sosa
authors.initials: LA
authors.lastname: León
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKinley
authors.forename: Robin M
authors.initials: RM
authors.lastname: McAllen
authors.forename: Clive N
authors.initials: CN
authors.lastname: May
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D001921:Brain / Q000187:drug effects; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000097:blood; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007262:Infusions, Intravenous; D007267:Injections; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects*; D008901:Mineralocorticoids; D012756:Sheep; D013997:Time Factors
chemical_list: D004573:Electrolytes; D006728:Hormones; D008901:Mineralocorticoids; D000450:Aldosterone