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Voltage-independent calcium channels mediate lipopolysaccharide-induced hyporeactivity to endothelin-1 in the rat aorta.
- Source :
-
American Journal of Physiology: Heart & Circulatory Physiology . May2009, Vol. 296 Issue 5, pH1408-H1415. 8p. - Publication Year :
- 2009
-
Abstract
- El-Awady MS, Smirnov SV, Watson ML. Voltage-independent calcium channels mediate lipopolysaccharide-inducëd hyporeactivity to endothelin-l in the rat aorta. Am J Physiol Heart Circ Physiol 296: H1408-H1415, 2009. First published March 13, 2009; doi:l0.l 152/ajpheart.01305.2008.-The roles of intracellu1ar calcium concentration ([Ca[sup2+]]1) and Ca[sup2+] sensitization in lipopolysaccharide (LPS)-induced vascular smooth muscle (VSM) hyporesponsiveness are incompletely understood. To investigate these roles, contraction responses to endothelin-l (ET-1) and 80 mM KCI; relaxation responses to nifedipine; the expression levels of mRNAs of ET-l and its receptors (ETA or ETB); the expression levels of protein kinase C (PKC) and phosphorylation of Rho kinase (ROKα), CPI-17, and myosin phosphatase target subunit-i (MYPT1); and changes in aortic VSM cell [Ca[sup2+]][subi] were measured in LPS-treated aortic rings from male Wistar rats (250-300 g). LPS (10 μg/ml, 20 h) decreased contraction induced by ET-l (0.3-100 nM) or 80 mM KCl. LPSinduced hypocontractility was not observed in the absence of external Ca[sup2+] but LPS-treated aorta remained hypocontractile on subsequent stepwise restoration of extracellular Ca[sup2+] (0.01-10 mM). Vascular relaxation to nifedipine; mRNA expression levels of ET1, ET[subA], or ET[subB] protein expression levels of PKC; and phosphorylation levels of ROKa, CPI-17, and MYPT1 were not affected by LPS. In isolated aortic VSM cells, ET-1 caused a transient initial increase iii [Ca[sup2+]][subi], followed by a maintained tonic increase in [Ca[sup2+]][subi], which was decreased by LPS pretreatment and was dependent on external Ca[sup2+]. Subsequent restoration of extracellular Ca[sup2+] increased [Ca[sup2+]][subi], but this increase was lower in the LPS-treated group. This difference in response to extracellular Ca[sup2+] addition was not affected by diltiazem, but was abolished by SKF-96365. Therefore, LPS induces hyporeactivity to ET-l in rat aorta that depends on external Ca[sup2+] influx through non-voltage-operated Ca[sup2+] channels, but not on ET-1 receptor expression or Ca[sup2+] sensitization. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636135
- Volume :
- 296
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Heart & Circulatory Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 40078955
- Full Text :
- https://doi.org/10.1152/ajpheart.01305.2008