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Comparative Effects of Nω-Nitro-L-Arginine, Nω-Nitro-L-Arginine Methyl Ester, and Nω-Nitro-L-Arginine Benzyl Ester on Vasodilator Responses to Acetylcholine and Substance P

  • David Y. Cheng
  • Bracken J. DeWitt
  • Timothy J. McMahon
  • Jose A. Santiago
  • Dennis B. McNamara
  • Philip J. Kadowitz

Abstract

Recent evidence suggests that the endothelium-derived relaxing factor first described by Furchgott and Zawadski (1980) is nitric oxide or a labile nitroso derivative. Nitric oxide is formed from L-arginine in cultured endothelial cells, and NG-monomethyl-L-arginine (L-NMMA) was the first L-arginine analog shown to inhibit nitric oxide formation (Moncada et al., 1989). Since the discovery that L-NMMA inhibits nitric oxide synthase, a number of L-arginine analogs that block nitric oxide release have been developed (Ishii et al., 1990; Moore et al., 1990). The use of these compounds has provided important information on the role of nitric oxide in the regulation of cardiovascular function in in vivo experiments (Bellan et al., 1991;1993; McMahon et al, 1991; McMahon and Kadowitz, 1992,1993). Experiments with nitric oxide synthase inhibitors, including Nω-nitro-L-arginine (L-NA) and Nω-nitro-L-arginine methyl ester (L-NAME), have provided evidence that nitric oxide is involved in maintaining the pulmonary and peripheral vascular bed in a dilated state and in mediating vasodilator responses to acetylcholine, bradykinin, substance P, and other nitric oxide releasing agents (Bellan et al., 1991,1993; McMahon et al., 1991; McMahon and Kadowitz, 1993). However, recent studies have shown that L-NAME and other alkyl esters of L-NA are muscarinic receptor antagonists and suggest that these compounds are poor choices as nitric oxide synthase inhibitors in studies in which muscarinic receptors are not blocked (Buxton et al., 1992). Although L-NAME has been reported to inhibit responses to acetylcholine, bradykinin, and substance P in the pulmonary vascular bed of the cat, other studies show that L-NAME does not inhibit responses to endothelium-dependent vasodilator agents (Lippton et al., 1992).

Keywords

Nitric Oxide Muscarinic Receptor Alkyl Ester Vasodilator Response Systemic Arterial Pressure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • David Y. Cheng
    • 1
  • Bracken J. DeWitt
    • 1
  • Timothy J. McMahon
    • 1
  • Jose A. Santiago
    • 1
  • Dennis B. McNamara
    • 1
  • Philip J. Kadowitz
    • 1
  1. 1.Department of PharmacologyTulane University Schoolof MedicineNew OrleansUSA

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