Flow modulation of agonist (ATP)-response (Ca2+) coupling in vascular endothelial cells

R. O. Dull, P. F. Davies

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

ATP-induced increases of intracellular calcium concentration ([Ca2+](i)) were measured as a function of flow rate in single cell recordings within a confluent endothelial cell monolayer. Although flow and its associated shear stress did not per se significantly alter basal [Ca2+](i), ATP-induced [Ca2+](i) was exquisitely sensitive to flow. Step increases of flow in the presence of ATP triggered large [Ca2+](i) transients that slowly (60-150 s) returned to basal values. ATP-releasable [Ca2+](i) was mobilized from intracellular stores, as well as obtained from the extracellular medium. Since potent ectonucleotidases on the cell surface are expected to influence local ATP concentrations, experiments were repeated using the poorly hydrolyzable ATP analogue β,γ-methyleneadenosine 5'-triphosphate (AMP-PCP). Comparison between ATP and AMP-PCP responses suggested that flow regulates the mass transport of agonist to the endothelial cell surface by overcoming the local effects of degradative enzymes. An additional, quite different phenomenon of flow-mediated [Ca2+](i) regulation in endothelial cells was observed when [Ca2+](i) oscillations induced by AMP-PCP in the absence of flow were shown to be reversibly inhibited by step increases in flow. These results imply that the effectiveness of local or systemic agonists in stimulating endothelial transduction will vary with flow rates. Regional variations in hemodynamic shear stresses associated with altered flow patterns throughout the arterial system are predicted to result in large variations of vessel wall responsiveness to physiological and pathological agonists.

Original languageEnglish (US)
Pages (from-to)H149-H154
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume261
Issue number1 30-1
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Blood flow
  • Cell calcium
  • Shear stress
  • Vascular tone

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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