Inhibition of nitric oxide formation by guanidines

Khalid Hasan, Bart Jeroen Heesen, John A. Corbett, Michael L. McDaniel, Katherine Chang, Wanda Allison, Bruce H R Wolffenbuttel, Joseph R. Williamson, Ronald Tilton

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Aminoguanidine, N,N′-diaminoguanidine, methylguanidine, and 1,1-dimethylguanidine were compared to NG-monomethyl-L- arginine (L-NMMA) for their ability to inhibit nitric oxide (NO) formation by cytokine-inducible and vascular constitutive isoforms of NO synthase. These comparisons were performed by assessing (1) cytokine-induced production of nitrite by RINm5F cells, (2) vasoconstrictor responses of isolated rat mesenteric arteries, and (3) in vivo blood pressure responses following intravenous bolus injection into anesthetized rats. Aminoguanidine and L-NMMA were the most potent inhibitors of cytokine-induced NO formation in RINm5F cells, while the other guanidine compounds were 10 (1,1-dimethylguanidine) to 100 (methylguanidine) times less potent. L-NMMA and 1,1-dimethylguanidine were the most potent inhibitors of the vascular constitutive isoform of NO synthase in both assay systems, while aminoguanidine and N,N′-diaminoguanidine were the least potent. These results (1) confirm the selective inhibition of the inducible isoform of NO synthase by aminoguanidine, (2) indicate that N,N′-diaminoguanidine, while ∼ 30 times less potent than aminoguanidine in inhibiting inducible NO synthase, has very little effect on constitutive NO synthase activity, and (3) 1,1-dimethylguanidine, like L-NMMA, is a relatively potent inhibitor of both isoforms of NO synthase.

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalEuropean Journal of Pharmacology
Volume249
Issue number1-2
DOIs
StatePublished - Nov 2 1993
Externally publishedYes

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Guanidines
omega-N-Methylarginine
Nitric Oxide
Nitric Oxide Synthase
Protein Isoforms
Methylguanidine
Nitric Oxide Synthase Type II
Cytokines
Blood Vessels
Mesenteric Arteries
Guanidine
Vasoconstrictor Agents
Nitrites
Intravenous Injections
pimagedine
Blood Pressure
N,N-dimethylguanidine
diaminoguanidine

Keywords

  • (L-NMMA)
  • 1,1-Dimethylguanidine
  • Aminoguanidine
  • Methylguanidine
  • N,N′-Diaminoguanidine
  • N-Monomethyl-L-arginine
  • Nitric oxide (NO)
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Hasan, K., Heesen, B. J., Corbett, J. A., McDaniel, M. L., Chang, K., Allison, W., ... Tilton, R. (1993). Inhibition of nitric oxide formation by guanidines. European Journal of Pharmacology, 249(1-2), 101-106. https://doi.org/10.1016/0014-2999(93)90667-7

Inhibition of nitric oxide formation by guanidines. / Hasan, Khalid; Heesen, Bart Jeroen; Corbett, John A.; McDaniel, Michael L.; Chang, Katherine; Allison, Wanda; Wolffenbuttel, Bruce H R; Williamson, Joseph R.; Tilton, Ronald.

In: European Journal of Pharmacology, Vol. 249, No. 1-2, 02.11.1993, p. 101-106.

Research output: Contribution to journalArticle

Hasan, K, Heesen, BJ, Corbett, JA, McDaniel, ML, Chang, K, Allison, W, Wolffenbuttel, BHR, Williamson, JR & Tilton, R 1993, 'Inhibition of nitric oxide formation by guanidines', European Journal of Pharmacology, vol. 249, no. 1-2, pp. 101-106. https://doi.org/10.1016/0014-2999(93)90667-7
Hasan K, Heesen BJ, Corbett JA, McDaniel ML, Chang K, Allison W et al. Inhibition of nitric oxide formation by guanidines. European Journal of Pharmacology. 1993 Nov 2;249(1-2):101-106. https://doi.org/10.1016/0014-2999(93)90667-7
Hasan, Khalid ; Heesen, Bart Jeroen ; Corbett, John A. ; McDaniel, Michael L. ; Chang, Katherine ; Allison, Wanda ; Wolffenbuttel, Bruce H R ; Williamson, Joseph R. ; Tilton, Ronald. / Inhibition of nitric oxide formation by guanidines. In: European Journal of Pharmacology. 1993 ; Vol. 249, No. 1-2. pp. 101-106.
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N2 - Aminoguanidine, N,N′-diaminoguanidine, methylguanidine, and 1,1-dimethylguanidine were compared to NG-monomethyl-L- arginine (L-NMMA) for their ability to inhibit nitric oxide (NO) formation by cytokine-inducible and vascular constitutive isoforms of NO synthase. These comparisons were performed by assessing (1) cytokine-induced production of nitrite by RINm5F cells, (2) vasoconstrictor responses of isolated rat mesenteric arteries, and (3) in vivo blood pressure responses following intravenous bolus injection into anesthetized rats. Aminoguanidine and L-NMMA were the most potent inhibitors of cytokine-induced NO formation in RINm5F cells, while the other guanidine compounds were 10 (1,1-dimethylguanidine) to 100 (methylguanidine) times less potent. L-NMMA and 1,1-dimethylguanidine were the most potent inhibitors of the vascular constitutive isoform of NO synthase in both assay systems, while aminoguanidine and N,N′-diaminoguanidine were the least potent. These results (1) confirm the selective inhibition of the inducible isoform of NO synthase by aminoguanidine, (2) indicate that N,N′-diaminoguanidine, while ∼ 30 times less potent than aminoguanidine in inhibiting inducible NO synthase, has very little effect on constitutive NO synthase activity, and (3) 1,1-dimethylguanidine, like L-NMMA, is a relatively potent inhibitor of both isoforms of NO synthase.

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