Author: Jianyu Tang, Lily Cooper, Meilin Gao, Zhen Lin
Research Article
LPS Differentially Affects Vasoconstrictor Responses: A Potential Role for RGS16
Meilin Gao1*, Jianyu Tang2, Zhen Lin3 and Lily Cooper2
1Department of Biochemistry, Xiamen University, Xiamen, China
2Department of Immunology, Harbin Medical University, Harbin, China
3Department of Microbiology, Shandong University, Jinan, China
Published: 22 February 2016
Abstract
Background: Sepsis-induced circulatory shock is marked by systemic vasodilation and reduced responsiveness to vasoconstrictors, contributing to high mortality rates. Lipopolysaccharide (LPS), a component of Gram-negative bacterial walls, plays a central role in this vascular dysfunction. The heterogeneity of LPS effects on vascular contractility may depend on specific G-Protein Coupled Receptor (GPCR) pathways. Regulators of G-protein Signaling (RGS) proteins, especially RGS16, modulate GPCR signaling and may influence these responses.
Objective: To investigate whether LPS differentially affects vascular responses to vasoconstrictors acting via Gαq-coupled receptors and whether these effects are associated with changes in RGS16 expression.
Methods: Isolated rat aortic rings were treated ex vivo with LPS (1 µg/mL, 4 hours). Concentration-response curves were generated for phenylephrine (PE), angiotensin II (Ang II), and endothelin-1 (ET-1). RGS16 expression was analyzed using qPCR and Western blotting.
Results: LPS significantly reduced PE-induced vasoconstriction, enhanced Ang II responses, and had minimal effects on ET-1 at low doses. RGS16 mRNA and protein levels were markedly upregulated in LPS-treated vascular smooth muscle.
Conclusion: LPS induces receptor-specific alterations in vasoconstriction, likely mediated by RGS16 upregulation. RGS16 may contribute to selective vascular hyporesponsiveness observed in septic shock.
Keywords: Lipopolysaccharide (LPS); Sepsis; Vasoconstriction; Vascular Smooth Muscle; G-protein Coupled Receptors (GPCRs); Regulator of G-protein Signaling 16 (RGS16); Phenylephrine; Angiotensin II; Endothelin-1; Vascular Hyporesponsiveness.
