Endocrine Abstracts

Angiotensin II (A-II) stimulates aldosterone (aldo) secretion through the zona glomerulosa AT1R. A-II can be metabolized to angiotensin III (A-III) which also stimulates aldo synthesis. In the rat A-III stimulates aldo secretion through the AT2R receptor.

The human adrenocortical HAC15 cells were incubated with A-II or A-III (10 nM) for 24 h and the concentration of aldo and cortisol (F) measured in the media. A-II produced a fourfold and A-III a twofold increase in aldo in the media. A-II produced a twofold increase in F concentration in the media, but A-III did not change F production. Losartan 10 μM inhibited the A-II and A-III stimulated production of aldo, but the AT2R antagonist PD123319 had no effect. Both A-II and A-III stimulated the expression of StAR, CYP11B1 and CYP11B2 mRNA. While A-II had no effect on CYP17A1 mRNA expression, A-III inhibited its expression.

HAC15 cells were incubated with 100 nM of A-II and A-III for 0.5, 1, 3 and 6 h, the media was extracted and angiotensin metabolites measured by HPLC–MS. Approximately 30% of A-II remained after 1 h incubation and was not detectable after 6 h. A-II was converted to angiotensin 1–7, angiotensin-IV and angiotensin 3–7, but not to A-III. A-III was decreased to ~40% after 30 min and was undetectable after 1 h. A small amount of the A-III was converted to angiotensin 3–7 and angiotensin-IV.

Addition of more A-II (10 nM) at 1, 3, 6 or 12 h did not increase aldo production at 24 h further compared to cells stimulated only once with A-II (10 nM) at time 0.

In conclusion, A-II is not converted to A-III in HAC15 cells. A-III stimulates aldo, but not cortisol production: A-II stimulates both. The half-life of A-II and A-III in the media is short, but stimulation of steroidogenesis persists.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.