Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors

作者：Briet Marie; Barhoumi Tlili; Mian Muhammad Oneeb Rehman; Coelho Suellen C; Ouerd Sofiane; Rautureau Yohann; Coffman Thomas M; Paradis Pierre; Schiffrin Ernesto L^*

来源：Hypertension, 2016, 67(5): 897-905.

DOI：10.1161/HYPERTENSIONAHA.115.07074

• inflammation
• mineralocorticoids
• oxidative stress
• potassium channels
• calcium-activated
• sodium
• vascular remodeling

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 approximate to 30 mm Hg in WT mice and approximate to 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.

• 出版日期2016-5
• 单位河北医科大学; McGill