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).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bellan, J.A., McNamara, D.B., and Kadowitz, P.J., 1993, Differential effects of nitric oxide synthesis inhibitor on vascular resistance and responses to acetylcholine in the cat, Am. J. Physiol. 264 (Heart Circ. Physiol. 33):H45.
Bellan, J.A., Minkes, R.K. McNamara, D.B., and Kadowitz, P.J., 1991, Nω-nitro-L-arginine selectively inhibits vasodilator responses to acetylcholine and bradykinin in cats, Am. J. Physiol. 260 (Heart Circ. Physiol. 29):H1025.
Broten, T.P., Miyashiro, J.K., Moncada, S., and Feigl, E.O., 1992, Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation, Am. J. Physiol. 262 (Heart Circ. Physiol. 31):H1519.
Buxton, I.L.O., Cheek, D.J., Eckman, D., Westfall, D.P., Sanders, K.M., and Keef, K.D., 1992, NG-nitro-L-arginine ester and other alkyl esters of arginine are muscarinic receptor antagonists, Circ. Res. 72:387.
Furchgott, R.F., and Zawadski, J.V., 1980, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature (Lond.) 288:373.
Gardiner, S.M., and Bennett, T., 1992, Involvement of nitric oxide in the regional haemodynamic effects of perindoprilat and captopril in hypovolemic brattleboro rats, Br. J. Pharmacol. 107:1181.
Huber, S., Grohs, J.G., Schwarzacher, S., and Raberger, G., 1992, Oral NG-nitro-L-arginine in conscious dogs: 24 hour hypertensive response in relation to plasma levels, Amino Acids 2:225.
Ishii, K., Chang, B., Kerwin, J.F., Huang, Z.J., and Murad, F., 1990, Nω-nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation, Eur. J. Pharmacol. 179:219.
Krejcy, K., Schwarzacher, S., and Raberger, G., 1993, Distribution and metabolism of NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester in canine blood in vitro, Naunyn-Schmiedeberg’s Arch. Pharmacol. 347:342.
Lippton, H.L., Hao, Q., and Hyman, A., 1992, L-NAME enhances pulmonary vasoconstriction without inhibiting EDRF-dependent vasodilation, J. Appl. Physiol. 73:2432.
McMahon, T.J., Hood, J.S., Bellan, J.A., and Kadowitz, P.J., 1991, Nω-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin, J. Appl.Physiol. 71:2026.
McMahon, T.J., and Kadowitz, P.J., 1992, Pulmonary vasodilator responses to vagal stimulation is blocked by Nω-nitro-L-arginine methyl ester in the cat, Circ. Res. 70:364.
McMahon, T.J., and Kadowitz, P.J., 1993, Analysis of responses to substance P in the pulmonary vascular bed of the cat, Am. J. Physiol. 264 (Heart Circ. Physiol. 35):H394.
Moncada, S., Palmer, R.M.J., and Higgs, E.A., 1989, Biosynthesis of nitric oxide from arginine. A pathway for the regulation of cell function and communication, Biochem. Pharmacol. 38:1709.
Moore, P.K., Al-Swayeh, O.A., Chong, N.W.S., Egands, R.A., and Gibson, A., 1990, L-Nω-nitroarginine (L-NOARG), a novel L-arginine-reversible inhibitor Nω of endothelium-dependent vasodilation in vitro, Br. J. Pharmacol. 99:408.
Santiago, J.A., Garrison, E.A., and Kadowitz, P.J., 1994, Comparative effects of N-nitro-L-arginine and NW -nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P, Eur. J. Pharmacol. 254:207.
Smith, R.E., Palmer, R.M., Bucknall, C.A., and Moncada, S., 1992, Role of nitric oxide synthesis in the regulation of coronary vascular tone in the isolated perfused rabbit heart, Heart Cardiovasc. Res. 26:508.
White, D.G., Gurden, J.M., Penny, D.M., Roach, A.G., and Watts, I.S., 1993, The effect of NG-nitro-L-arginine methyl ester upon basal blood flow and endothelium-dependent vasodilation in the dog hindlimb, Br. J. Pharmacol. 108:763.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Cheng, D.Y., DeWitt, B.J., McMahon, T.J., Santiago, J.A., McNamara, D.B., Kadowitz, P.J. (1995). 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. In: Weissman, B.A., Allon, N., Shapira, S. (eds) Biochemical, Pharmacological, and Clinical Aspects of Nitric Oxide. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1903-4_16
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1903-4_16
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5777-3
Online ISBN: 978-1-4615-1903-4
eBook Packages: Springer Book Archive