Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

Thomas P. Misko; William M. Moore; Thomas P. Kasten; G. Allen Nickols; John A. Corbett; Ronald G. Tilton; Michael L. McDaniel; Joseph R. Williamson; Mark G. Currie

doi:10.1016/0014-2999(93)90357-N

Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

Thomas P. Misko, William M. Moore, Thomas P. Kasten, G. Allen Nickols, John A. Corbett, Ronald G. Tilton, Michael L. McDaniel, Joseph R. Williamson, Mark G. Currie

Research output: Contribution to journal › Article › peer-review

695 Scopus citations

Abstract

Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell and enzyme-based measurements we have shown that aminoguanidine is equipotent to N^G-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.

Original language	English (US)
Pages (from-to)	119-125
Number of pages	7
Journal	European Journal of Pharmacology
Volume	233
Issue number	1
DOIs	https://doi.org/10.1016/0014-2999(93)90357-N
State	Published - Mar 16 1993
Externally published	Yes

Keywords

Aminoguanidine
Nitric oxide synthase
Selective inhibitor inducible

ASJC Scopus subject areas

Pharmacology

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10.1016/0014-2999(93)90357-N

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title = "Selective inhibition of the inducible nitric oxide synthase by aminoguanidine",

abstract = "Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell and enzyme-based measurements we have shown that aminoguanidine is equipotent to NG-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.",

keywords = "Aminoguanidine, Nitric oxide synthase, Selective inhibitor inducible",

author = "Misko, {Thomas P.} and Moore, {William M.} and Kasten, {Thomas P.} and Nickols, {G. Allen} and Corbett, {John A.} and Tilton, {Ronald G.} and McDaniel, {Michael L.} and Williamson, {Joseph R.} and Currie, {Mark G.}",

note = "Funding Information: The able technical assistance of Franklin Kent Hamra is gratefully appreciated This work was supported by National Institutes of Health Grants DK-06181 (M L M ), T32 DKO-07296 (J A C ), EY-06600 and HL-39934 (J R W ) and American Heart Association Grant 900885 (G A N )",

year = "1993",

month = mar,

day = "16",

doi = "10.1016/0014-2999(93)90357-N",

language = "English (US)",

volume = "233",

pages = "119--125",

journal = "European Journal of Pharmacology",

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T1 - Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

AU - Misko, Thomas P.

AU - Moore, William M.

AU - Kasten, Thomas P.

AU - Nickols, G. Allen

AU - Corbett, John A.

AU - Tilton, Ronald G.

AU - McDaniel, Michael L.

AU - Williamson, Joseph R.

AU - Currie, Mark G.

N1 - Funding Information: The able technical assistance of Franklin Kent Hamra is gratefully appreciated This work was supported by National Institutes of Health Grants DK-06181 (M L M ), T32 DKO-07296 (J A C ), EY-06600 and HL-39934 (J R W ) and American Heart Association Grant 900885 (G A N )

PY - 1993/3/16

Y1 - 1993/3/16

N2 - Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell and enzyme-based measurements we have shown that aminoguanidine is equipotent to NG-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.

AB - Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell and enzyme-based measurements we have shown that aminoguanidine is equipotent to NG-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.

KW - Aminoguanidine

KW - Nitric oxide synthase

KW - Selective inhibitor inducible

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Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

Abstract

Keywords

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