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.