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

  • M. C. Hendriks-Balk
  • M. Tjon-Atsoi
  • N. Hajji
  • A. E. Alewijnse
  • S. L. M. PetersEmail author
Article

Abstract

The profound hypotension in septic shock patients is difficult to treat as it is accompanied by depressed constrictor responses to α1-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 μg/ml) for 22 hours differentially affected agonist-induced contractile responses at four distinct G-protein coupled receptors (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 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.

Keywords

Regulator of G protein signalling Lipopolysaccharide Vasoconstriction Aorta 

Diversos efectos vasoconstrictores del LPS: un posible papel para RGS16?

Resumen

El lipopolisacárido bacteriano LPS está implicado en la mayor parte de las alteraciones cardiovasculares propias del shock séptico. Se investiga en este trabajo sobre los efectos de la exposición al LPS en la contractilidad vascular en general y sobre el papel de las proteínas reguladoras de la señalización de proteínas G (RGS) en las alteraciones vasculares inducidas por el LPS. La exposición (22 h) de anillos aórticos de rata a diversas concentraciones de LPS (3, 10, 30 μg/ml) afecta de forma diferencial las respuestas contráctiles inducidas por la activación de 4 diferentes receptores acoplados a proteínas G (α1-adrenorreceptores, de angiotensina II, de serotonina y ET-1 de endotelina). Asi, el pretratamiento con LPS no afecta la contracción inducida por endotelina, mientras que reduce la de fenilefrina y angiotensina II e incrementa la de serotonina. Además, el tratamiento con LPS aumenta la expresión de RNAm de RGS16 tanto en anillos aórticos como en células VSMC, pero no de RNAm de RGS2, RGS3, RGS4 y RGS5. Los cambios de RNAm de RGS16 podrían contribuir a la regulación diferencial de las respuestas contráctiles a los vasoconstrictores en presencia de LPS.

Palabras clave

Regulador de señalización de proteína G Lipopolisacárido Vasoconstricción Aorta 

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Copyright information

© Universidad de Navarra 2009

Authors and Affiliations

  • M. C. Hendriks-Balk
    • 1
  • M. Tjon-Atsoi
    • 1
  • N. Hajji
    • 1
  • A. E. Alewijnse
    • 1
  • S. L. M. Peters
    • 1
    Email author
  1. 1.Department of Pharmacology & PharmacoltherapyAcademic Medical CenterAmsterdamThe Netherlands

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