Angiotensin 1–7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo
Angiotensin (1–7) [Ang 1–7] is a 7 amino acid peptide generated predominantly from Ang II by the action of Ang-converting enzyme 2. We previously showed that Ang 1–7 reduced plasma aldosterone and plasma renin activity in high fructose–fed rats, and that the reduction in circulating aldosterone seemed to accord a parallel reduction in plasma renin activity. Here, we tested the possibility that Ang 1–7 affects aldosterone secretion acting directly in glomerulosa cells. First, as detected by immunofluorescence, the receptor for Ang 1–7, Mas1 is localized predominantly at the rat adrenal subcapsular region. Second, in isolated rat glomerulosa cells incubates, Ang 1–7 attenuated the aldosterone response to Ang II, with the strongest effect seen on Ang II (10−9 M) (control 22±2.5 pg/105 cells; Ang II [10−9 M] 189±11 pg/105 cells; Ang II [10−9 M]+Ang 1–7 [10−6 M] 33±3.6 pg/105 cells; P<0.001) and the largest effect on adrenocorticotropic hormone (10−8 M) (control 30±3.4 pg/105 cells; ACTH [10−8 M] 409±32.5 pg/105 cells; ACTH [10−8 M]+Ang 1–7 [10−6 M] 280±12.5 pg/105 cells; P<0.001). In contrast, Ang 1–7 did not affect the aldosterone response to potassium (K+). In rats subjected to a low-salt diet for 7 days, continuous infusion of Ang 1–7 (576 μg/kg per day) resulted in a lesser rise in aldosterone (salt deplete+Ang 1–7, 16.4±4.8 ng/dL) compared with rats receiving vehicle (salt deplete+vehicle, 27.6±5.3 ng/dL; P<0.01) but did not modify plasma renin activity. Taken together, these results indicate that Ang 1–7 can act as a negative modulator of aldosterone secretion in vitro and in vivo.
- Received January 7, 2016.
- Revision received January 12, 2016.
- Accepted May 3, 2016.
- © 2016 American Heart Association, Inc.