Effects of L-NA and sodium nitroprusside on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in hamster cheek pouch venules.

Abstract

Our objective was to study how the topical application of a nitric oxide synthase inhibitor (l-NA, Nomega-nitro-L-arginine) and a nitric oxide donor, sodium nitroprusside (SNP), could modulate leukocyte adhesion (sticking) and microvascular permeability as altered by ischemia/reperfusion (I/R) and topically applied histamine after I/R. Golden hamsters were prepared for intravital microscopy. Ischemia was induced by an inflatable silicon rubber cuff mounted around the neck of the cheek pouch prepared for intravital microscopy. Saline, L-NA, sodium nitroprusside, and histamine were applied in the superfusion solution. FITC-dextran was injected iv 30 min before initiation of ischemia as a marker of microvascular permeability. L-NA 10(-5) M inhibited both the increase in number of sticking leukocytes and the increase in vascular permeability after I/R compared with the untreated control group of hamsters. SNP neutralized this effect of L-NA on leukocytes and vascular permeability and caused arteriolar dilation at the concentration used, 10(-6) M. Both SNP and L-NA + SNP enhanced the I/R-induced macromolecular leakage. The topical application of SNP and SNP + L-NA did not modify the response to histamine after I/R compared with the untreated control group. In hamsters not subjected to I/R, histamine-induced macromolecular leakage was inhibited by L-NA and L-NA + SNP but was unchanged by SNP. It is concluded that inhibition of nitric oxide formation by L-NA reduced both leukocyte adhesion in postcapillary venules and the increase in macromolecular leakage and that a NO donor such as SNP could enhance the macromolecular leakage response to I/R.

• Authors: C Simões, E Svensjö, E Bouskela
• Journal: Microvascular research (Microvasc Res) Vol. 62 Issue 2 Pg. 128-35 (Sep 2001) ISSN: 0026-2862 [Print] United States
• PMID: 11516241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Enzyme Inhibitors
• Nitric Oxide Donors
• Vasodilator Agents
• Nitroprusside
• Nitroarginine
• Nitric Oxide
• Histamine

Topics

• Animals
• Cell Adhesion (physiology)
• Cheek (blood supply)
• Cricetinae (physiology)
• Enzyme Inhibitors (pharmacology)
• Histamine (administration & dosage, pharmacology)
• Leukocytes (metabolism)
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Donors (pharmacology)
• Nitroarginine (administration & dosage, pharmacology)
• Nitroprusside (administration & dosage, pharmacology)
• Reperfusion Injury (physiopathology)
• Vasodilator Agents (pharmacology)
• Venules (drug effects, metabolism)