1590436

pubmed:Citation

5 Pt 2

As previously reported, NG-monomethyl-L-arginine (L-NMMA) constricted pial arterioles, inhibited dilation of pial arterioles by acetylcholine (ACh) or L-arginine (L-Arg), and enhanced platelet adhesion/aggregation at sites of endothelial damage. However, all of these effects were inhibited by local application of 20 micrograms/ml indomethacin (Indo). When 100 micrograms/ml acetylsalicylic acid were used instead of Indo, the acid also blocked the effects of L-NMMA. Superoxide dismutase (SOD; 50 U/ml) blocked the constriction produced by L-NMMA and also blocked the constriction produced by N omega-nitro-L-arginine (NNA). SOD also prevented L-NMMA from blocking dilation by ACh. SOD itself had no effect on diameter or on the response to ACh, norepinephrine, or BaCl2. The effects of L-NMMA and of Indo were also selective. Thus L-NMMA did not inhibit dilation by prostacyclin or bradykinin, and Indo did not inhibit dilation by prostacyclin. Indo did not interfere with the ability of arginase to enhance platelet adhesion/aggregation or with the ability of ACh or L-Arg to inhibit adhesion/aggregation. We conclude that in mouse cerebral microcirculation the ability of L-NMMA and NNA to constrict arterioles, the ability of L-NMMA to inhibit dilation by ACh or L-Arg and the ability of L-NMMA to enhance platelet adhesion/aggregation are all related to interference with phenomena dependent on "classical" endothelium-derived relaxing factor (EDRFACh). However, in this preparation the action of L-NMMA or NNA may not be due to competitive inhibition of the enzyme producing EDRFACh from L-Arg. Rather, L-NMMA and NNA appear to activate cyclooxygenase with resultant production of superoxide, which inactivates EDRFACh.

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MEDLINE

0002-9513

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H1343-9

pubmed-meshheading:1590436-Animals, pubmed-meshheading:1590436-Arginine, pubmed-meshheading:1590436-Aspirin, pubmed-meshheading:1590436-Blood Platelets, pubmed-meshheading:1590436-Cell Adhesion, pubmed-meshheading:1590436-Cerebrovascular Circulation, pubmed-meshheading:1590436-Cyclooxygenase Inhibitors, pubmed-meshheading:1590436-Free Radical Scavengers, pubmed-meshheading:1590436-Indomethacin, pubmed-meshheading:1590436-Male, pubmed-meshheading:1590436-Mice, pubmed-meshheading:1590436-Mice, Inbred ICR, pubmed-meshheading:1590436-Microcirculation, pubmed-meshheading:1590436-Nitroarginine, pubmed-meshheading:1590436-Platelet Aggregation, pubmed-meshheading:1590436-Superoxide Dismutase, pubmed-meshheading:1590436-Vasodilation, pubmed-meshheading:1590436-Vasodilator Agents, pubmed-meshheading:1590436-omega-N-Methylarginine

L-NMMA in brain microcirculation of mice is inhibited by blockade of cyclooxygenase and by superoxide dismutase.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't