**1. Introduction**

Recent research efforts on the mineralocorticoid receptor (MR) signaling have revealed a cluster of new pathophysiological mechanism mediated by vascular MR in which aldosterone (Aldo) plays a pivotal role; however, the molecular pathways are not completely elucidated. In this chapter, we review and discuss novel contributions about the structure, ligand activation, and additional mechanisms that confer selectivity for Aldo of the MR in vascular tissues. In addition, we review the fine-tuning that the MR exerts on the expression and function of

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ion channels that participate in Ca2+ handling of vascular smooth muscle cells and the therapeutic implications for hypertension and cardiovascular diseases.

least three variants of MR mRNA (α, β, and γ) are encoded in a tissue-specific manner under

Mineralocorticoid Receptor in Calcium Handling of Vascular Smooth Muscle Cells

http://dx.doi.org/10.5772/intechopen.79556

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The MR receptor has the same protein structure as other members of the nuclear receptor superfamily. The MR is composed of an A/B domain (1–604 aa) with a transactivation function and several serine and threonine phosphorylation sites [7] and a DNA binding domain (DBD, 604–699 aa) with two zinc finger motifs that recognize DNA-specific sequences named hormone response elements (HRE), normally found in the promoters of target genes [8]. After the DBD, the hinge D region (670–733 aa) is found and, finally, the C-terminal region (734–981 aa) that is harboring the ligand-binding domain (LBD) with a pocket (which comprises Asp767, Gln773, Arg814, and Thr942) involved in the recognition of agonist and

The direct and specific actions of Aldo require MR expression in target tissues. For a long time, it was thought that MR was expressed exclusively in kidney epithelial cells and that Aldo was secreted only by the adrenal gland. However, a cumulative evidence has showed the presence of MR in non-epithelial tissues, such as the colon, salivary glands, trachea, heart [10], adipocytes [11], brain [5], skeletal muscle [12], leucocytes, macrophages [13], and vessels

H]Aldo bindings [10, 16, 19, 21, 22]

the control of different gene promoters [6].

**2.1. Mineralocorticoid receptor expression in different tissues**

**Tissue or cell type Detection method Reference** Kidney NB [5] Gut (gastrointestinal tract) NB [20] Brain NB [5] Hippocampus NB [5] Heart Im [10] Skeletal muscle WB [12] Endothelial cells RT-PCR [17]

*Carotid artery* Im [10] *Cerebral artery* WB [18] *Coronary artery* RT-PCR, Im, WB [10, 16, 19] *Humeral artery* Im [10] *Mesenteric artery* Im, RT-PCR, WB [10, 15, 19] *Pulmonary artery* Im, NB [10, 14] *Renal artery* Im [10] *Saphenous vein* RT-PCR, WB, WB [23]

antagonist [9] (**Figure 1**).

[14–19] (**Table 1**).

Vascular tissues

*Aorta* Im, WB, [<sup>3</sup>

In 1972, Crabbé demonstrated that Aldo was interacting with cytoplasmic receptors and that the steroid-protein complex acted as activator triggering the synthesis of mRNA and proteins [1]; thus, Aldo was the first identified mammalian steroid hormone that exerted transcriptional actions via some kind of cytoplasmic/nuclear receptors [2]. Several classes of mineralocorticoid receptors were identified in both epithelial and surprisingly in non-epithelial tissues such as cardiomyocytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) [2], auguring the future actions of Aldo in the cardiovascular system.
