AI Article Synopsis
- The study investigates the effects of mineralocorticoids and their receptors in regulating vascular tone and blood pressure during septic conditions.
- Research was conducted using both mouse models and human vascular cells, focusing on changes in receptor expression following treatment with aldosterone and inflammatory cytokines.
- Findings indicate that aldosterone enhances survival and blood pressure in endotoxic shock by restoring receptor expressions, while sepsis-related factors diminish these receptors in both mice and human cells.
Article Abstract
Objectives: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock.
Design: Experimental study.
Setting: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients.
Subjects: Adult male C57Black 6 mice, adult patients with septic shock.
Interventions: Mice were injected with lipopolysaccharide and/or aldosterone. Human endothelial and smooth muscle cells were treated with pro-inflammatory cytokines with or without aldosterone, nuclear factor-κB inhibitor BAY 11-7082, or plasma from septic patients.
Measurements And Main Results: Aldosterone improved 5-day survival, invasive arterial pressure, and in vivo and ex vivo arterial response to phenylephrine at 18 hours after induction of murine endotoxic shock. Both α1-adrenoceptor and mineralocorticoid receptor expressions studied in mouse aortas were down-regulated at 6 and 18 hours in endotoxemic mice and restored in aldosterone-treated mice. Furthermore, tumor necrosis factor-α decreased both mineralocorticoid receptor and α1-adrenoceptor expressions within 5 hours in human vascular cells in a nuclear factor-κB pathway-dependent manner. Mineralocorticoid receptor expression was also blunted in human cells treated with plasma from septic patients.
Conclusion: We found a beneficial effect of mineralocorticoids on survival, blood pressure, and vascular reactivity, associated with a restoration of α1-adrenoceptor expression in endotoxic shock. Furthermore, blunted vascular mineralocorticoid receptor expression might participate in hemodynamic failure during sepsis.
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| http://dx.doi.org/10.1097/CCM.0000000000002462 | DOI Listing |
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