Angiotensin 1–7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo. Issue 2 (August 2016) - Shefer, Gabi
Abstract : 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/10 5 cells; Ang II [10 −9 M] 189±11 pg/10 5 cells; Ang II [10 −9 M]+Ang 1–7 [10 −6 M] 33±3.6 pg/10 5 cells; P <0.001) and the largest effect on adrenocorticotropic hormone (10 −8 M) (control 30±3.4 pg/10 5 cells; ACTH [10 −8 M] 409±32.5 pg/10 5 cells; ACTH [10 −8 M]+Ang 1–7 [10 −6 M] 280±12.5 pg/10 5 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.