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Activation of endothelial nitric oxide synthase by proanthocyanidin-rich fraction from Croton celtidifolius (Euphorbiaceae): involvement of extracellular calcium influx in rat thoracic aorta.
- Source :
-
Journal of pharmacological sciences [J Pharmacol Sci] 2008 Jun; Vol. 107 (2), pp. 181-9. - Publication Year :
- 2008
-
Abstract
- The present study investigates the mechanisms related to the endogenous nitric oxide synthase (eNOS) activation in the relaxant effects of a proanthocyanidin-rich fraction (PRF), obtained from Croton celtidifolius Baill barks, in rat thoracic aorta rings with endothelium. In vessels pre-contracted with phenylephrine (Phe), PRF (0.1 - 100 microg/mL) induced a concentration-dependent relaxation. This effect was significantly reduced by endothelium denudation, by N(omega)-nitro-L-arginine, and by 1H[1,2,3]oxadiazolo[4,3-alpha]quinoxalin. However, the vasorelaxant effect was not altered by indomethacin, atropine, tetraethylammonium, and charybdotoxin plus apamin. In thoracic aorta rings pre-contracted with phorbol-12,13-dibuyrate, PRF also induced a concentration-dependent relaxation. The PRF-induced relaxation disappeared in the absence of extracellular calcium in the medium and decreased significantly in the presence of lanthanum. A sulfhydryl alkylating agent, N-ethylmaleimide, and a phospholipase C (PLC) blocker, neomycin, significantly decreased PRF-induced vasorelaxation. In vessels pre-contracted with Phe, the PRF-induced vasorelaxant effect was not altered by quinacrine and ONO-RS-082, genistein and thyrphostin A-23, GF109203, and pertussis toxin and cholera toxin. The results suggest that the PRF-induced vasorelaxant effect is endothelium-dependent and involves the NO/cGMP pathway. We hypothesize that the activation of eNOS is due to an increase of intracellular calcium derived from PLC activation and an N-ethylmaleimide sensitive pathway.
- Subjects :
- Animals
Dose-Response Relationship, Drug
Enzyme Activation
Ethylmaleimide pharmacology
In Vitro Techniques
Male
Nitric Oxide physiology
Nitroarginine pharmacology
Rats
Rats, Wistar
Type C Phospholipases physiology
Aorta, Thoracic metabolism
Calcium metabolism
Croton chemistry
Nitric Oxide Synthase Type III metabolism
Proanthocyanidins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1347-8613
- Volume :
- 107
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 18566521
- Full Text :
- https://doi.org/10.1254/jphs.fp0072385