[PP.25.06] ANGIOTENSIN-(1–7) PEPTIDE AND MAS RECEPTOR AND ANGIOTENSIN II- TYPE 2 RECEPTOR ARE INVOLVED IN ALDOSTERONE AND CORTISOL PRODUCTION IN HUMAN ADRENOCORTICAL CELL LINE (NCI-H295)

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Abstract

Objective:

Aldosterone and cortisol secretion are tightly regulated by angiotensin II (Ang II) acting via angiotensin type 1 receptor (AT1R) in adrenal tissue. In several tissues, AT2R and the MasR, target of Ang-(1–7), can counteregulate AT1R effects. Nevertheless, whether AT2R and MasR play any role in the adrenal cortex is still unknown.

Objective:

Aim: To investigate: 1) the presence of AT2R and MasR in human adrenocortical tissue 2) if Ang-(1–7) could play a role in modulation of aldosterone and cortisol production in a human adrenocortical cell line (NCI-H295) in vitro.

Design and method:

RT-PCR, immunoblotting, and immunohistochemistry were used to detect AT2R and MasR Moreover, in NCI-H295 cells, we used Ang-(1–7) to stimulate MasR, Ang II to stimulate AT1R and AT2R, irbesartan and A779 as blockers for AT1R and MasR respectively. RT-PCR was used to quantify CYP11B1/CYP11B2 genes expression.

Results:

AT2R and MasR are heterogeneously expressed in human adrenal cortex and in APA. Ang-(1–7) had no effect at low concentrations after 12 hours, although at high concentrations it significantly increased CYP11B1 and CYP11B2 transcriptional expression compared to control, and affected AngII effects. A779 did not significantly blunt the effects of Ang-(1–7) at high doses whereas irbesartan abolished these effects.

Conclusions:

These results showed the expression of AT2R and MasR in human adrenal cortex, albeit at much lower levels than the AT1R.

Conclusions:

They suggested a role of high local concentrations of Ang-(1–7) in the modulation of aldosterone and cortisol production.

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