Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors. Issue 5 (May 2016)

• Record Type: Journal Article
• Authors: Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C.; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M.; Paradis, Pierre; Schiffrin, Ernesto L.
• Is Part Of: Hypertension. Volume 67:Issue 5(2016:May)
• Publication Date: 2016-05
• Subjects: inflammation -- mineralocorticoids -- oxidative stress -- potassium channels, calcium-activated -- sodium -- vascular remodeling; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.115.07074
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors in Agtr1a −/− and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure (BP) by ≈30 mm Hg in WT mice and ≈50 mm Hg in Agtr1a −/− mice. Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed in Agtr1a −/− mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in WT and Agtr1a −/− mice. Agtr1a −/− mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting that sodium retention could contribute to the exaggerated BP rise induced by aldosterone. Agtr1a −/− mice had decreased mesenteric artery expression of the calcium-activated potassium channel Kcnmb1, which may enhance myogenic tone and together with sodium retention, exacerbate BP responses to aldosterone/salt in Agtr1a −/− mice. We conclude that although aldosterone activation of mineralocorticoid receptors raises BP more in Agtr1a −/− mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction. Abstract : Supplemental Digital Content is available in the text.