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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Senejoux, François Girard-Thernier, Corine Berthelot, Alain Bévalot, Françoise Demougeot, Céline |
| Description | Country affiliation: France Author Affiliation: Senejoux F ( EA 3185 Fonctions et Dysfonctions Epithéliales, UFR des Sciences Médicales et Pharmaceutiques, 25030 Besançon, France.) |
| Abstract | Apocynin is a naturally occurring acetophenone widely used as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Recent data suggested that apocynin might exert NADPH oxidase-independent pharmacological properties. Among them, vasorelaxant properties have been described, but the mechanisms still give rise to debates. The present study investigated the mechanisms involved in the vasorelaxant effect of apocynin on the in vitro model of rat isolated thoracic aortic rings. Apocynin (30 µM to 10 mM) induced a dose-dependent relaxation in both endothelium-intact and endothelium-denuded aortic rings with respective EC50 values of 0.78 ± 0.08 and 1.91 ± 0.21 mM. Endothelium removal or inhibition of nitric oxide (NO) synthase with N(ω)-nitro-L-arginine-methyl ester (L-NAME) significantly decreased but did not abolish the effect of apocynin. By contrast, apocynin-induced relaxation was unchanged after incubation with indomethacin or charybdotoxin plus apamin. In endothelium-denuded aortas, the vasorelaxant effect of apocynin was significantly reduced by glibenclamide but not by 4-aminopyridine nor by iberiotoxin. Apocynin significantly decreased Ca(2+)-induced contraction and inhibited intracellular Ca(2+) mobilization after contraction with phenylephrine. Finally, the acute intravenous injection of apocynin led to an immediate and transient hypotensive effect in spontaneously hypertensive rats (SHR). In conclusion, our data demonstrated that apocynin induces both endothelium-independent relaxant effects involving inhibition of Ca(2+) mobilization and activation of KATP channels in vascular smooth muscle cells and endothelium-dependent effects mediated by NO. These results should provide a basis for caution when interpreting results on the vascular effects of apocynin. |
| File Format | HTM / HTML |
| ISSN | 07673981 |
| Issue Number | 3 |
| Volume Number | 27 |
| e-ISSN | 14728206 |
| Journal | Fundamental & Clinical Pharmacology |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2013-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Acetophenones Pharmacology Aorta, Thoracic Drug Effects Vasodilation Vasodilator Agents Administration & Dosage Animals Antihypertensive Agents Metabolism Calcium Dose-response Relationship, Drug Endothelium, Vascular Hypertension Drug Therapy Injections, Intravenous Katp Channels Male Muscle, Smooth, Vascular Cytology Nitric Oxide Rats Rats, Inbred Shr Rats, Wistar Vasoconstriction Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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