HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1408    most recent 01305.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by El-Awady, M. S. H. Articles by Watson, M. L. Search for Related Content PubMed PubMed Citation Articles by El-Awady, M. S. H. Articles by Watson, M. L.

Voltage-independent calcium channels mediate lipopolysaccharide-induced hyporeactivity to endothelin-1 in the rat aorta

Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom

Submitted 19 December 2008 ; accepted in final form 10 March 2009

The roles of intracellular calcium concentration ([Ca²⁺]_i) and Ca²⁺ sensitization in lipopolysaccharide (LPS)-induced vascular smooth muscle (VSM) hyporesponsiveness are incompletely understood. To investigate these roles, contraction responses to endothelin-1 (ET-1) and 80 mM KCl; relaxation responses to nifedipine; the expression levels of mRNAs of ET-1 and its receptors (ET_A or ET_B); the expression levels of protein kinase C (PKC) and phosphorylation of Rho kinase (ROK), CPI-17, and myosin phosphatase target subunit-1 (MYPT1); and changes in aortic VSM cell [Ca²⁺]_i 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-1 (0.3–100 nM) or 80 mM KCl. LPS-induced hypocontractility was not observed in the absence of external Ca²⁺, but LPS-treated aorta remained hypocontractile on subsequent stepwise restoration of extracellular Ca²⁺ (0.01–10 mM). Vascular relaxation to nifedipine; mRNA expression levels of ET-1, ET_A, or ET_B; protein expression levels of PKC; and phosphorylation levels of ROK, CPI-17, and MYPT1 were not affected by LPS. In isolated aortic VSM cells, ET-1 caused a transient initial increase in [Ca²⁺]_i, followed by a maintained tonic increase in [Ca²⁺]_i, which was decreased by LPS pretreatment and was dependent on external Ca²⁺. Subsequent restoration of extracellular Ca²⁺ increased [Ca²⁺]_i, but this increase was lower in the LPS-treated group. This difference in response to extracellular Ca²⁺ addition was not affected by diltiazem, but was abolished by SKF-96365. Therefore, LPS induces hyporeactivity to ET-1 in rat aorta that depends on external Ca²⁺ influx through non-voltage-operated Ca²⁺ channels, but not on ET-1 receptor expression or Ca²⁺ sensitization.

calcium sensitization; sepsis; vascular smooth muscle