Agents that modify EDRF formation alter antiplatelet properties of brain arteriolar endothelium in vivo

H. Nishimura, W. I. Rosenblum, G. H. Nelson, S. Boynton

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

In the presence of circulating Evans blue a helium-neon laser injuries the endothelium of brain surface arterioles in situ. The injury is known to selectively eliminate endothelium-dependent responses. The present study documents in mice the fact that such endothelial sites become selectively attractive to passing platelets that have been activated as a result of more severe injury upstream. We then test the hypothesis that the ''capture'' of platelets at the downstream site is due to loss of ''classical'' endothelial-dependent relaxing factor of acetylcholine (EDRF(ACh)) at that site. EDRF(ACh) is known to inhibit platelet adhesion/aggregation and is synthesized from L-arginine. We show that agents that would either enhance or reduce the synthesis of local EDRF(ACh) reduce or increase the incidence of capture as predicted by the hypothesis. Thus N(G)-monomethyl-L-arginine (L-NMMA) and arginase that would reduce synthesis of EDRF(ACh) enhanced platelet capture. L-Arginine, which would enhance synthesis of EDRF(ACh), inhibited platelet capture. In addition, L-NMMA and arginase enhanced platelet aggregation over the more severely damaged site upstream from the site of capture. Ex vivo studies of platelets harvested from treated mice showed that the platelets themselves were unaffected by the treatments that, except for arginase given intravenously, all involved topical application of the tested drugs.

Original languageEnglish
Pages (from-to)H15-H21
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume261
Issue number1 30-1
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Arginase
  • Cerebral microcirculation
  • Endothelial injury
  • Endothelial-dependent relaxing factor
  • L-arginine
  • N(G)-monomethyl-L-arginine
  • Platelet adhesion/aggregation

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