Pre-clinical data on the role of mineralocorticoid receptor antagonists in reversing vascular inflammation

Abstract

Aldosterone plays an important role in regulating extracellularvolume, and is the downstream modulator of the renin-angiotensin-aldosterone system. In addition, aldosterone also causes increased oxidative stress and decreased nitric oxide bioavailability that results in vascular inflammation. Aldosterone therefore functions to promote cardiovascular damage and remodelling not only in a blood pressuredependent manner but also in a blood pressure-independent manner. Abundant experimental evidence from animal models has documented the mechanisms whereby aldosterone causes these effects as well as the benefits of mineralocorticoid receptor (MR) blockade to reduce vascular inflammation. The anti-inflammatory effects of MR antagonism seen in clinical trials suggest that MR blockade will be an important therapeutic approach in the future.

Δ-9,11 Modification of Glucocorticoids Dissociates Nuclear Factor-κB Inhibitory Efficacy from Glucocorticoid Response Element-Associated Side Effects

“…Given the relatively high affinities of VBP1 and anecortave for MR and the known anti-inflammatory activities of MR complexes (Yagi and Sata, 2011), we tested the abilities of prednisolone and anecortave to induce MR gene targets in normal and mdx myotubes. The mRNA profiles used to analyze GR targets were queried for known MR gene targets, and the data were analyzed statistically, visualized by heat maps, and tested for MR-associated networks using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA).…”