Septic shock: A role for RGS proteins?

Abstract

The profound hypotension in septic shock patients is difficult to treat as they display depressed vascular responses to α‐adrenergic agonists. Bacterial lipopolysaccharide (LPS) is the main trigger for most of the cardiovascular alterations occurring in septic shock. Recently, LPS‐induced cardiac failure was found to be associated with upregulation of the Regulator of G protein Signalling (RGS) proteins RGS4 and RGS16 (Cardiovasc Res 53:156, 2002).In this study we investigate the effects of LPS exposure on vascular contractility in general and the role of RGS proteins in the LPS‐induced vascular alterations.Exposure of rat aortic rings to various LPS concentrations (1, 3, 10, 30 μg ml−1) for 22 hours had differential effects on the contractile responses to agonists at four distinct G‐protein coupled receptors. Phenylephrine‐ and angiotensin II‐induced contraction was reduced whereas serotonin‐induced contraction was enhanced. The endothelin‐1‐induced contraction was unaffected. Concomitantly, LPS treatment increased the RGS16 mRNA expression level both in aortic rings and cultured vascular smooth muscle cells (VSMCs) but RGS2, RGS3, RGS4 and RGS5 was unaffected. Regulation of RGS16 mRNA in VSMCs was also time‐ and concentration‐dependent. The changes in RGS16 mRNA might contribute to the differential regulation of the contractile responses in an LPS model of septic shock.