title: Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension.
abstract: BACKGROUND
  Endothelin (ET)-1 contributes to raising blood pressure (BP) and inducing cardiovascular disease by vasoconstriction and potent stimulation of aldosterone secretion. In the rat this latter effect occurs via ET(B) receptors; in humans in vitro studies implicated both ET(A) and ET(B) receptors, but there is no conclusive evidence in vivo.
  
  
  METHODS
  We recruited 13 consenting hypertensive patients: six with primary aldosteronism (PA) and seven with high-to-normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min for 5 min followed by 100 nmol/min for 10 min) of the ET(A)-selective antagonist BQ-123 either alone or, on a different day, together with an identical dose of the ET(B)-selective antagonist BQ-788. Plasma aldosterone, cortisol and ACTH concentration and plasma renin activity (PRA) were measured with radioimmunoassay at -15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively.
  
  
  RESULTS
  BQ-123 alone and combined with BQ-788 significantly lowered mean BP in both PA and HNRH patients (by 6-10 mmHg at nadir; P<0.01). In PA patients, a short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (-14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788 lowered aldosterone (-39 and -28%, respectively) and PRA (-43 and -16%, respectively), while cortisol and ACTH were unaffected.
  
  
  CONCLUSIONS
  Endogenous ET-1 contributes to maintaining the high BP values and the aldosterone secretion in both PA and HNRH patients. In the former patients, the aldosterone secretagogue effect of ET-1 is mediated via ET(B) receptors, while in the latter it occurs mainly via ET(A)-mediated stimulation of renin production.
authors.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 4, University Hospital, via Giustiniani 2, 35126 Padova, Italy. gianpaolo.rossi@unipd.it
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
authors.forename: Chiara
authors.initials: C
authors.lastname: Ganzaroli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cesari
authors.forename: Andrea
authors.initials: A
authors.lastname: Maresca
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Gastone G
authors.initials: GG
authors.lastname: Nussdorfer
authors.forename: Achille C
authors.initials: AC
authors.lastname: Pessina
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood*; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006929:Hyperaldosteronism / Q000097:blood / Q000188:drug therapy*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D012083:Renin / Q000097:blood*
chemical_list: D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; C086539:BQ 788; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D006854:Hydrocortisone