Aldosterone and cortisol synthesis regulation by angiotensin-(1-7) and angiotensin-converting enzyme 2 in the human adrenal cortex.
Journal
Journal of hypertension
ISSN: 1473-5598
Titre abrégé: J Hypertens
Pays: Netherlands
ID NLM: 8306882
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
pubmed:
4
3
2021
medline:
16
10
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
The branch of the renin--angiotensin system constituting angiotensin-(1-7) [Ang-(1-7)], the Ang II type 2 receptor, the Mas receptors and the Ang-(1-7)-forming enzyme ACE-2, by counteracting the Ang II type 1 receptor (AT1R)-mediated effects, are held to be cardiovascular protective in several conditions. However, whether Ang-(1-7) and ACE-2 are detectable in human adrenocortical tissues and whether they affect aldosterone and cortisol biosynthesis was unknown. We measured angiotensin peptides with liquid chromatography tandem-mass spectrometry and ACE-2 mRNA with digital droplet (dd)PCR in human aldosterone-producing adenoma (APA) and APA-adjacent tissue obtained from patients with primary aldosteronism. We also investigated the effects of Ang-(1-7) and the ACE-2 activator diminazene aceturate (DIZE) on aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) gene expression, in the absence or presence of the AT1R antagonist irbesartan, or of the MasR antagonist A779. APA and APA-adjacent adrenocortical tissues express ACE-2 mRNA and contain detectable amounts of Ang II and Ang-(2-8), but not of Ang I, Ang-(1-5), Ang (3-8) and Ang-(1-7). Under unstimulated and Ang II- stimulated conditions Ang-(1-7) did not blunt CYP11B1 and CYP11B2 mRNA. At supraphysiological concentrations (10-4 mol/l), Ang-(1-7) stimulated both CYP11B1 and CYP11B2 mRNA via the AT1R. The ACE-2 activator DIZE increased by 1.5-fold ACE-2 mRNA but did not blunt Ang II- upregulated CYP11B1 and CYP11B2 expression. These results do not support the hypothesis that the ACE-2/Ang-(1-7)/MasR axis play a protective role by counteracting enhanced aldosterone secretion in humans.
Identifiants
pubmed: 33657582
doi: 10.1097/HJH.0000000000002816
pii: 00004872-202108000-00013
pmc: PMC9904433
doi:
Substances chimiques
MAS1 protein, human
0
Peptide Fragments
0
Proto-Oncogene Mas
0
Angiotensin II
11128-99-7
Aldosterone
4964P6T9RB
Angiotensin I
9041-90-1
Cytochrome P-450 CYP11B2
EC 1.14.15.4
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
angiotensin I (1-7)
IJ3FUK8MOF
Hydrocortisone
WI4X0X7BPJ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1577-1585Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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