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Hypercholesterolemia enhances oxidant production in mesenteric venules exposed to Ischemia/Reperfusion.

Abstract
It has been shown that hypercholesterolemia (HCh) exaggerates the microvascular dysfunction that is elicited by ischemia and reperfusion (I/R). The objective of this study was to determine whether oxidants contribute to the exaggerated inflammatory responses and enhanced albumin leakage observed in HCh rat mesenteric venules exposed to I/R (10 minutes of ischemia and 30 minutes of reperfusion). Intravital videomicroscopy was used to quantify the number of adherent and emigrated leukocytes, albumin extravasation, platelet-leukocyte aggregation in postcapillary venules, and the degranulation of adjacent mast cells. Oxidation of the fluorochrome dihydrorhodamine 123 (DHR) was used to monitor oxidant production by venular endothelium. I/R was shown to elicit an increased DHR oxidation in venules of both control and HCh rats, with the latter group exhibiting a significantly larger response. Treatment with either oxypurinol or superoxide dismutase largely prevented the leukocyte recruitment, platelet-leukocyte aggregation, mast cell degranulation, and enhanced DHR oxidation elicited by I/R in HCh rats. The enhanced albumin leakage was reduced by superoxide dismutase but not by oxypurinol. These results indicate that HCh amplifies the oxidant stress elicited by I/R and that interventions that blunt the oxidant stress effectively attenuate the leukocyte, platelet, and mast cell activation that result from I/R.
AuthorsI Kurose, R E Wolf, M B Grisham, D N Granger
JournalArteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 18 Issue 10 Pg. 1583-8 (Oct 1998) ISSN: 1079-5642 [Print] United States
PMID9763530 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Albumins
  • Enzyme Inhibitors
  • Oxidants
  • Rhodamines
  • dihydrorhodamine 123
  • Superoxide Dismutase
  • Oxypurinol
Topics
  • Albumins (metabolism)
  • Animals
  • Cell Adhesion
  • Enzyme Inhibitors (pharmacology)
  • Hypercholesterolemia (blood, metabolism)
  • Leukocytes (metabolism)
  • Male
  • Mesenteric Arteries (metabolism)
  • Oxidants (metabolism)
  • Oxypurinol (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (metabolism)
  • Rhodamines (metabolism)
  • Superoxide Dismutase (metabolism, pharmacology)

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