Impaired agonist-stimulated intracellular free calcium (Ca i) responses in aortic endothelial cells freshly dispersed from endotoxemic guinea pigs

J. J. Jones, M. Sturek, O. Zhong, H. R. Adams, J. L. Parker

Research output: Contribution to journalArticle


We recently reported evidence for impairment of endothelium-dependent relaxation (EDR) and decreased agonist-stimulated endothelial synthesis/release of nitric oxide (NO) using in vitro aortic and coronary preparations isolated from endotoxemic guinea pigs. We tested the hypothesis that impaired EUR involves dysfunctional endothelial Ca i regulation by using fura-2 microfluorometry to compare agonist-stimulated Ca i responses of endothelial cells (EC) 16 h after intmperiloneal injection of bacterial endotoxin (LPS; 4 mg/kg] or saline (CON). Basal Ca i (340/380 nm fluorescence ratio. R) was not different in CON and LPS EC (1.1±.03 and 1.1±03 respectively). Exposure of EC to ADP (10 μM), in the presence of extracellular Ca 2+ (2mM) produced hiphasic increases in Ca i that were markedly decreased (P<0.05) in EC from LPS-treated animals. Peak ADP-stimulated Ca, responses (R) averaged 2.2 ± .21 in CON EC and 1.5 ±.11 in EC from LPS-treated animals. Exposure of the same EC to acetylcholine (ACh; 10 μM) produced sustained increases in Ca (R=1.4±13) in CON EC; however, LPS abolished Ca i responses to ACh. Moreover. ACh (but not ADP) Ca i responses rapidly decreased with time (within 2 h) after dispersion. In conclusion, our data demonstrate impaired agonist -stimulated endothelial Ca i mobilization; the dependence of NO synthesis on Ca i suggests that Ca, defects may contribute to LPS-induced impaired EDR.

Original languageEnglish (US)
Pages (from-to)A77
JournalFASEB Journal
Issue number3
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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