Adrenal endothelin-1 levels are not associated with aldosterone secretion in primary aldosteronism.
BACKGROUND
Endothelin-1 (ET-1) may function as an aldosterone secretagogue and, in turn, aldosterone can upregulate ET-1 expression. Hence, the existence of a feedforward loop involving ETs and aldosterone has been speculated in primary aldosteronism (PA). In the present study, we sought to examine ET-1 secretion from the adrenal glands in patients with PA.


METHODS
We determined ET-1 levels in blood samples obtained during adrenal venous sampling of patients affected by PA (n=17). Furthermore, we examined the mRNA expression of the ET system in tissue samples from aldosterone-producing adenomas (APAs, n=9) and control normal adrenals (n=3).


METHODS
Blood ET-1 levels were determined by RIA. Tissue mRNA expression of the ET system was assayed with Affymetrix microarrays.


RESULTS
ET-1 levels did not differ between inferior vena cava and adrenal vein blood in both bilateral adrenal hyperplasia and APA patients. Moreover, cortisol-normalized ET-1 levels did not show lateralized adrenal ET-1 secretion in APAs. Through gene expression profiling with microarray performed in a distinct set of APA individuals (n=9), we confirmed the adrenal expression of a complete ET system, but we did not detect a significant upregulation of ET components within the APA tissue compared with normal adrenals.


CONCLUSIONS
The present data argue against the hypothesis of increased ET-1 secretion from APAs and do not support a general role for adrenal ET-1 in the vascular pathophysiology of PA.
Morello
F
F
Fourth Division of Internal Medicine and Hypertension Unit, San Giovanni Battista Hospital of Torino, University of Torino, Torino, Italy. fulvio.morello@unito.it
Schiavone
D
D
Mengozzi
G
G
Bertello
C
C
Liew
C C
CC
Bisbocci
D
D
Mulatero
P
P
Veglio
F
F
D000236:Adenoma / Q000378:metabolism / Q000503:physiopathology; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000503:physiopathology; D000311:Adrenal Glands / Q000378:metabolism*; D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D000450:Aldosterone; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes