title: Angiotensin 1-7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo.
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.
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Gabi
authors.initials: G
authors.lastname: Shefer
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Yonit
authors.initials: Y
authors.lastname: Marcus
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Esther
authors.initials: E
authors.lastname: Knoll
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Oleg
authors.initials: O
authors.lastname: Dolkart
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Shulamit
authors.initials: S
authors.lastname: Foichtwanger
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Nava
authors.initials: N
authors.lastname: Nevo
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.).
authors.forename: Rona
authors.initials: R
authors.lastname: Limor
authors.affiliation: From the Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel (G.S., Y.M., E.K., S.F., R.L., N.S.); Division of Orthopedic Surgery, Shoulder Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (O.D.); and Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (N.N.). naftalis@tlvmc.gov.il.
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D015384:Zona Glomerulosa / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; C000715470:MAS1 protein, human; C000715472:Mas1 protein, rat; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D000450:Aldosterone; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: aldosterone; aldosterone-system; angiotensin; angiotensins; fructose; hypertension; renin