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.
Hendriks-Balk
M C
MC
Department of Pharmacology & Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands.
Tjon-Atsoi
M
M
Hajji
N
N
Alewijnse
A E
AE
Peters
S L M
SL
D000818:Animals; D002478:Cells, Cultured; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D008070:Lipopolysaccharides; D020710:RGS Proteins; C107413:RGS16 protein; D012333:RNA, Messenger; D019331:NG-Nitroarginine Methyl Ester