Effects of L-NA and sodium nitroprusside on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in hamster cheek pouch venules.
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.
Simões
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Laboratório de Pesquisas em Microcirculação, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, Rio de Janeiro, 20550-013, Brazil.
Svensjö
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Bouskela
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D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014699:Venules / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine