Faculty Collaboration Database

Inhibition of nitric oxide formation by guanidines. Eur J Pharmacol 1993 Nov 02;249(1):101-6

Date

11/02/1993

Pubmed ID

7506664

DOI

10.1016/0014-2999(93)90667-7

Scopus ID

2-s2.0-0027374229 (requires institutional sign-in at Scopus site)   166 Citations

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 approximately 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.

Author List

Hasan K, Heesen BJ, Corbett JA, McDaniel ML, Chang K, Allison W, Wolffenbuttel BH, Williamson JR, Tilton RG

Author

John A. Corbett PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Oxidoreductases
Animals
Arginine
Blood Pressure
Cell Line
Guanidines
In Vitro Techniques
Interleukin-1
Male
Mesenteric Arteries
Methylguanidine
Nitric Oxide
Nitric Oxide Synthase
Nitrites
Rats
Rats, Sprague-Dawley
Vasoconstriction
omega-N-Methylarginine