title: Direct contribution of vascular mineralocorticoid receptors to blood pressure regulation.
abstract: Hypertension is an extremely prevalent cardiovascular risk factor and current antihypertensive therapies do not adequately treat hypertension in many affected individuals. Thus, a better understanding of mechanisms of hypertension could lead to novel therapies. Mineralocorticoid receptors (MR) are known to regulate blood pressure by responding to aldosterone in the kidney to regulate sodium retention. Recent evidence supports a direct contribution of the vasculature to control of BP and suggests the possibility that MR antagonists may also lower blood pressure by acting on extrarenal MR. This review summarizes existing research considering the role of the vascular MR in regulating vasoreactivity and blood pressure. Multiple studies indicate a role for vascular MR in modulating vasoconstriction and vasorelaxation. Activation of MR in vascular endothelial and smooth muscle cells leads to increased reactive oxygen species production and decreased availability of nitric oxide, important regulators of vascular reactivity. Transgenic mouse models, including an endothelial MR overexpressing mouse and a smooth muscle cell-specific MR-knockout mouse, support a direct role for vascular MR in control of blood pressure. This new evidence demonstrating that vascular MR directly contribute to control of vasoreactivity and blood pressure supports vascular MR and the pathways they control as novel therapeutic targets to treat hypertension.
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, USA; Sackler School of Biomedical Graduate Studies, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Kathleen V
authors.initials: KV
authors.lastname: Barrett
authors.forename: Amy T
authors.initials: AT
authors.lastname: McCurley
authors.forename: Iris Z
authors.initials: IZ
authors.lastname: Jaffe
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D017382:Reactive Oxygen Species; D018161:Receptors, Mineralocorticoid; D009569:Nitric Oxide
keywords: aldosterone; blood pressure; mineralocorticoid receptor; nitric oxide; reactive oxygen species; vasoreactivity