LPS differentially affects vasoconstrictor responses: a potential role for RGS16?

The profound hypotension in septic shock patients is difficult to treat as it is accompanied by depressed constrictor responses to alpha1-adrenoceptor agonists. Bacterial lipopolysaccharide (LPS) is the main trigger for most of the cardiovascular alterations occurring in septic shock. In this study we investigated the effects of LPS exposure on vascular contractility in general and the role of Regulator of G protein Signalling (RGS) proteins in the LPS-induced vascular alterations. Exposure of rat aortic rings to various LPS concentrations (3, 10, 30 microg/ml) for 22 hours differentially affected agonist-induced contractile responses at four distinct G-protein coupled receptors (alpha1-adrenoceptors, angiotensin II, serotonin and endothelin-1 receptors). While the endothelin-1-induced contraction was unaffected by LPS pre-treatment, phenylephrine- and angiotensin II-induced contraction were significantly reduced whereas serotonin-induced contraction was significantly enhanced. Concomitantly, LPS treatment increased the RGS16 mRNA expression both in aortic rings and cultured vascular smooth muscle cells (VSMCs) but not that of RGS2, RGS3, RGS4 or RGS5. The significant increase in RGS16 mRNA expression in VSMCs by LPS was time- and concentration-dependent but independent of increased inducible NO synthase (iNOS) activity. The changes in RGS16 mRNA might contribute to the differential regulation of the contractile responses to vasoconstrictors upon LPS exposure.

Diversos efectos vasoconstrictores del LPS: un posible papel para RGS16? / LPS differentially affects vasoconstrictor responses: a potential role for RGS16?

The profound hypotension in septic shock patients is difficult to treat as it isaccompanied by depressed constrictor responses to α1-adrenoceptor agonists. Bacteriallipopolysaccharide (LPS) is the main trigger for most of the cardiovascular alterationsoccurring in septic shock. In this study we investigated the effects of LPSexposure on vascular contractility in general and the role of Regulator of G proteinSignalling (RGS) proteins in the LPS-induced vascular alterations. Exposure of rataortic rings to various LPS concentrations (3, 10, 30 μg/ml) for 22 hours differentiallyaffected agonist-induced contractile responses at four distinct G-protein coupledreceptors (α1-adrenoceptors, angiotensin II, serotonin and endothelin-1 receptors).While the endothelin-1-induced contraction was unaffected by LPS pre-treatment,phenylephrine- and angiotensin II-induced contraction were significantly reducedwhereas serotonin-induced contraction was significantly enhanced. Concomitantly,LPS treatment increased the RGS16 mRNA expression both in aortic rings and culturedvascular smooth muscle cells (VSMCs) but not that of RGS2, RGS3, RGS4 orRGS5. The significant increase in RGS16 mRNA expression in VSMCs by LPS wastime- and concentration-dependent but independent of increased inducible NO synthase(iNOS) activity. The changes in RGS16 mRNA might contribute to the differentialregulation of the contractile responses to vasoconstrictors upon LPS exposure(AU)

El lipopolisacárido bacteriano LPS estáimplicado en la mayor parte de las alteracionescardiovasculares propias del shock séptico. Seinvestiga en este trabajo sobre los efectos de laexposición al LPS en la contractilidad vascularen general y sobre el papel de las proteínasreguladoras de la señalización de proteínas G(RGS) en las alteraciones vasculares inducidaspor el LPS. La exposición (22 h) de anillos aórticosde rata a diversas concentraciones de LPS(3, 10, 30 μg/ml) afecta de forma diferencial lasrespuestas contráctiles inducidas por la activaciónde 4 diferentes receptores acoplados (α1-adrenorreceptores, de angiotensinaII, de serotonina y ET-1 de endotelina).Asi, el pretratamiento con LPS no afecta lacontracción inducida por endotelina, mientrasque reduce la de fenilefrina y angiotensina II eincrementa la de serotonina. Además, el tratamientocon LPS aumenta la expresión deRNAm de RGS16 tanto en anillos aórticoscomo en células VSMC, pero no de RNAm deRGS2, RGS3, RGS4 y RGS5. Los cambios deRNAm de RGS16 podrían contribuir a laregulación diferencial de las respuestas contráctilesa los vasoconstrictores en presencia deLPS(AU)