Elsevier

Steroids

Volume 60, Issue 1, January 1995, Pages 120-124
Steroids

Paper
Aldosterone biosynthesis and action in vascular cells

https://doi.org/10.1016/0039-128X(94)00026-9Get rights and content

Abstract

In view of the hypothetical possibility that the vascular renin-angiotensin system (RAS) might include aldosterone biosynthesis and action in the vasculature, we have undertaken a study to identify aldosterone released into the perfusion circuit from the rat mesenteric artery, and to investigate the effects of an angiotensin converting enzyme inhibition (ACEI) on aldosterone production from the vasculature. After 30 min equilibration, 240 mL of perfusate was collected and subjected to reverse-phase HPLC and subsequent mass spectrometry. Mass spectra corresponding to authentic corticosterone and aldosterone were obtained from the samples of mesenteric artery perfusate. Production of aldosterone in the mesenteric artery was not changed by adrenalectomy, although it was reduced in the arterial perfusate from rats pretreated with ACEI. By RT-PCR the expression of CYP 11B2 and mineralocorticoid receptor genes were demonstrated in both vascular endothelial and smooth muscle cells. These studies constitute indirect evidence supporting our hypothesis that locally produced aldosterone in the vascular tissue acts on vascular tone and remodeling via a paracrine or autocrine manner.

References (15)

There are more references available in the full text version of this article.

Cited by (83)

  • Analysis of the gene polymorphism of aldosterone synthase (CYP11B2) and atrial natriuretic peptide (ANP) in women with preeclampsia

    2016, European Journal of Obstetrics and Gynecology and Reproductive Biology
    Citation Excerpt :

    The human gene of aldosterone synthase (CYP11B2) is composed of nine exons and eight introns [4]. Until recently it was thought that the CYP11B2 expression exists mainly in the zona glomerulosa of the adrenal gland, however studies in recent years showed the presence of gene expression of aldosterone synthase in the cardiac muscle [7–10], and also in endothelial and vascular smooth muscle cells [11,12]. Among the many polymorphisms of aldosterone synthase many studies have focused on the transversion of cytosine to thymine at position −344 located in CYP11B2 promoter, which is one of the more common DNA sequence variations of this gene [4,13].

  • Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist

    2015, European Journal of Pharmacology
    Citation Excerpt :

    Aldosterone, a steroid hormone secreted from the adrenal glands, binds to the mineralocorticoid receptor in epithelial cells of the distal tubule and collecting duct in the kidney, and regulates electrolyte homeostasis, body fluid and blood pressure (Marver and Kokko, 1983). In addition to such classical effects, it has been reported that mineralocorticoid receptor is also expressed in non-epithelial tissues such as renal mesangial cells (Nishiyama et al., 2005) and podocytes (Shibata et al., 2007), heart (Lombès et al., 1995), brain (Watzka et al., 2000), blood vessel (Takeda et al., 1995) and adipose tissue (Zennaro et al., 1998), and that the aldosterone/mineralocorticoid receptor pathway plays an important role in the pathogenesis of cardiovascular injury through direct enhancement of inflammation (Gilbert and Brown, 2010), oxidative stress (Fiebeler and Luft, 2005) and fibrosis (Young, 2008). Thus, the activation of the aldosterone/mineralocorticoid receptor pathway is considered to be one of risk factors for cardiovascular diseases.

  • Extra-adrenal glucocorticoid synthesis: Immune regulation and aspects on local organ homeostasis

    2013, Molecular and Cellular Endocrinology
    Citation Excerpt :

    Clearly, to resolve the action of locally produced GCs in the brain on brain functions, more studies are needed. It has been reported that ex vivo perfused blood vessels can convert pregnenolone to corticosterone and that perfused heart or blood vessels from adrenalectomized rats release corticosterone and aldosterone into the perfusate, suggesting an ability of the cardiovascular system to produce corticosteroids (Silvestre et al., 1998; Takeda et al., 1995, 1994). However, discrepancies in the literature regarding the expression in the cardiovascular system of the enzymes required for corticosteroid production exist with reports claiming a lack of expression of particularly CYP11B1 and CYP11B2 (Ahmad et al., 2004; Gomez-Sanchez et al., 2004; Young et al., 2001).

  • Mineralocorticoid receptors in vascular function and disease

    2012, Molecular and Cellular Endocrinology
    Citation Excerpt :

    Extra-adrenal synthesis of Aldo in tissues including the heart has also been reported (Silvestre et al., 1998; Slight et al., 1999). Expression of Aldo synthase (CYP11B2) and production of Aldo, was originally reported in vascular cells and vessels (Hatakeyama et al., 1994; Takeda et al., 1995a,b, 1996; Kayes-Wandover and White, 2000), however, subsequent studies have failed to demonstrate Aldo biosynthesis in the vasculature (Ahmad et al., 2004; Gomez-Sanchez et al., 2004; Jaffe and Mendelsohn, 2005) and the physiological relevance of vascular Aldo production remains controversial. Regardless of the Aldo source, it is now generally accepted that vascular cells contain functional MR capable of responding directly to Aldo through genomic and non-genomic mechanisms to regulate normal vascular function and contribute to cardiovascular disease.

View all citing articles on Scopus
View full text