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Titolo:
Role of L-arginine in the vascular actions and development of tolerance tonitroglycerin
Autore:
Abou-Mohamed, G; Kaesemeyer, WH; Caldwell, RB; Caldwell, RW;
Indirizzi:
Med Coll Georgia, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA Med CollGeorgia Augusta GA USA 30912 ol & Toxicol, Augusta, GA 30912 USA Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 asc Biol Ctr, Augusta, GA 30912 USA
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 130, anno: 2000,
pagine: 211 - 218
SICI:
0007-1188(200005)130:2<211:ROLITV>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; ENDOTHELIUM-DEPENDENT RELAXATION; SMOOTH-MUSCLE RELAXATION; GLYCERYL TRINITRATE; ORGANIC NITRATES; SUPEROXIDE ANION; CROSS-TOLERANCE; STABLE ANGINA; RAT AORTA; CELLS;
Keywords:
nitroglycerin; tolerance; L-arginine; nitric oxide synthase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Caldwell, RW Med Coll Georgia, Dept Pharmacol & Toxicol, 1120 15th St, Augusta, GA 30912 USA Med Coll Georgia 1120 15th St Augusta GA USA 30912 30912 USA
Citazione:
G. Abou-Mohamed et al., "Role of L-arginine in the vascular actions and development of tolerance tonitroglycerin", BR J PHARM, 130(2), 2000, pp. 211-218

Abstract

1 The goal of this work was to test the role of nitric oxide synthase (NOS) and its substrate L-arginine in development of tolerance to nitroglycerin's (GTN) vasodilator actions.2 GTN's effects on NOS activity and NO formation were tested in cultured bovine aortic endothelial cells (BAECs). The arginine to citrulline conversion assay showed that GTN stimulated NOS basal activity in BAECs by similar to 40%, comparable with acetylcholine (ACh)-treated controls. Both effects were blocked by L-NMMA. Photometric assays showed that both GTN and ACh-stimulated NO formation. Both effects were potentiated by L-arginine and inhibited by L-NAME. L-NAME inhibited ACh responses similar to 80% compared withsimilar to 40% for GTN responses.3 The aortic ring assay showed that 2 h pretreatment with GTN caused substantial tolerance to GTN's vasodilating effects as evidenced by a 38 fold rightward shift of the concentration-relaxation curve. In contrast to D-arginine, addition of L-arginine substantially inhibited this effect, reducing the rightward shift to 4.4 fold of control values. GTN tolerance was associated with a 40% reduction in L-arginine tissue levels. GTN had a biphasic effect on BAEC uptake of L-arginine, stimulating uptake at 5 and 15 min, and suppressing uptake after 1 and 4 h4 In summary, acute GTN treatment stimulates endothelial NOS activity in producing NO and increases cellular uptake of L-arginine. Prolonged GTN exposure reduces GTN's vasodilator actions, decreases L-arginine tissue levels and depresses BAECs uptake of L-arginine. Supplementation of L-arginine reduces development of GTN tolerance. These data indicate that GTN tolerance depends in part on activation of the NOS pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 00:42:20