Endothelin-1 and nitric oxide affect human cerebromicrovascular endothelial responses and signal transduction.

Y. Chen, R. M. McCarron, N. Azzam, J. Bembry, C. Reutzler, Frederick Lenz, M. Spatz

Research output: Contribution to journalArticle

Abstract

Endothelium plays a central role in regulating the vascular tone, blood flow and blood brain barrier (BBB) permeability. The experiments presented here examine the mechanisms by which nitric oxide (NO) and endothelin-1 (ET-1) may be involved in these processes. The findings indicate that ET-1-stimulated [Ca2+]i accumulation occurs through activation of ETA receptor. The capacity of NO to affect this response was indicated by results showing: 1) a two-fold increase in ET-1-stimulated [Ca2+]i by L-NAME, the inhibitor of nitric oxide synthase, and 2) a dose-dependent decrease in [Ca2+]i accumulation by pretreatment with Nor-1 (NO donor). Abrogation of this Nor-1 effect by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-pCPT-cGMPS (an inhibitor of protein kinase G) and inhibition of ET-1 stimulated intracellular Ca2+ accumulation by 8-bromo-cGMP (a permeable, analog of cGMP) substantiate the involvement of interplay between ET-1 and NO in [Ca2+]i accumulation in HBMEC. ET-1 treatment also increased thickness of F-actin cytoskeletal filaments in HBMEC. This effect was attenuated by pretreatment with NO; NO also rarefied F-actin filaments in control cultures. The findings support a linkage between NO and ET-1 in regulating microvascular tone, microcirculation and BBB permeability and indicate a role for cGMP/cGMP protein kinase system and cytoskeletal changes in responses of HBMEC.

Original languageEnglish (US)
Pages (from-to)131-135
Number of pages5
JournalActa Neurochirurgica, Supplement
Volume76
StatePublished - 2000
Externally publishedYes

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Endothelin-1
Signal Transduction
Nitric Oxide
Blood-Brain Barrier
Actin Cytoskeleton
Actins
Permeability
Cyclic GMP-Dependent Protein Kinases
Nitric Oxide Donors
Guanylate Cyclase
NG-Nitroarginine Methyl Ester
Microcirculation
Cytoskeleton
Nitric Oxide Synthase
Protein Kinases
Endothelium
Blood Vessels

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Neurology

Cite this

Endothelin-1 and nitric oxide affect human cerebromicrovascular endothelial responses and signal transduction. / Chen, Y.; McCarron, R. M.; Azzam, N.; Bembry, J.; Reutzler, C.; Lenz, Frederick; Spatz, M.

In: Acta Neurochirurgica, Supplement, Vol. 76, 2000, p. 131-135.

Research output: Contribution to journalArticle

Chen, Y. ; McCarron, R. M. ; Azzam, N. ; Bembry, J. ; Reutzler, C. ; Lenz, Frederick ; Spatz, M. / Endothelin-1 and nitric oxide affect human cerebromicrovascular endothelial responses and signal transduction. In: Acta Neurochirurgica, Supplement. 2000 ; Vol. 76. pp. 131-135.
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