Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation

Citation
Y. Kumagai et al., Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation, AM J P-REG, 281(1), 2001, pp. R25-R30
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
ISSN journal
0363-6119 → ACNP
Volume
281
Issue
1
Year of publication
2001
Pages
R25 - R30
Database
ISI
SICI code
0363-6119(200107)281:1<R25:PIEAAS>2.0.ZU;2-5
Abstract
Diesel exhaust particles cause an impairment of endothelium-dependent vasor elaxation and are associated with cardiopulmonary-related diseases and mort ality, but the mechanistic details are poorly understood. Since we reported previously that phenanthraquinone, an environmental chemical contained in diesel exhaust particles, suppresses neuronal nitric oxide synthase (nNOS) activity by shunting electrons away from the normal catalytic pathway, it w as hypothesized that phenanthraquinone inhibits endothelial NOS (eNOS) acti vity and affects vascular tone. Therefore, the effects of phenanthraquinone on eNOS activity, endothelium-dependent relaxation, and blood pressure wer e examined in the present study. Phenanthraquinone inhibited NO formation e valuated by citrulline formed by total membrane fraction of bovine aortic e ndothelial cells with an IC50 value of 0.6 muM. A kinetic study revealed th at phenanthraquinone is a competitive inhibitor with respect to NADPH and a noncompetitive inhibitor with respect to L-arginine. Endothelium-dependent relaxation of rat aortic rings by ACh was significantly inhibited by phena nthraquinone (5 muM), whereas the endothelium-independent relaxation by nit roglycerin was not. Furthermore, an intraperitoneal injection of phenanthra quinone (0.36 mmol/ kg) to rats resulted in an elevation of blood pressure (1.4-fold, P < 0.01); under this condition, plasma levels of stable NO meta bolites, nitrite/nitrate, in phenanthraquinone-treated rats was reduced to 68% of control levels. The present findings suggest that phenanthraquinone has a potent inhibitory action on eNOS activity via a similar mechanism rep orted for nNOS, thereby causing the suppression of NO-mediated vasorelaxati on and elevation of blood pressure.