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The Role of Endothelial Cell Mineralocorticoid Receptors in Blood Pressure Regulation and Vascular Function
Author(s) -
Barrett Mueller Katelee,
Bender Shawn,
Shahid Mohd,
Aronovitz Mark,
Kershaw Tanya,
Hill Michael,
Jaffe Iris
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.950.9
Subject(s) - endocrinology , medicine , aldosterone , vasoconstriction , mesenteric arteries , mineralocorticoid receptor , endothelial dysfunction , mineralocorticoid , angiotensin ii , phenylephrine , electrical impedance myography , blood pressure , vasodilation , artery
Vascular endothelial cells (EC) express mineralocorticoid receptor (MR) and contribute to vasoreactivity. Studies suggest EC MR may play a role in blood pressure (BP) control and vascular function. To address this, we made a mouse with EC MR deletion (EC MR KO). We confirmed EC‐specific MR deficiency, intact leukocyte MR expression and normal renal MR function. Characterization of BP phenotype by telemetry revealed EC‐MR deletion did not alter systolic, diastolic, circadian, or salt‐sensitive BP. Hypertensive response to renin angiotensin aldosterone pathway modulators – aldosterone + salt and angiotensin II (ang II) – were equal in EC MR KO and MR‐intact littermates. The role of EC MR in vasoconstriction was explored by wire myography in mesenteric arterioles showing no constriction difference to phenylephrine, KCl, endothelin 1, thromboxane agonist or ang II. EC dependent relaxation to acetylcholine and EC independent relaxation to sodium nitroprusside were unaffected by presence of EC MR in mesenteric, coronary, or basilar vessels in healthy mice. Yet the MR ligand aldosterone is elevated in patients with obesity and resistant hypertension and MR inhibitors improve EC function in those populations. In dyslipidemic ApoE KO mice, loss of EC MR seems to protect from high fat diet‐induced EC dysfunction. We conclude that in healthy mice, EC MR does not affect vasoreactivity or BP control and hypothesize that EC MR mediates vascular dysfunction induced by cardiac risk factors.