New insights into the mechanisms of the vasorelaxant effects of apocynin in rat thoracic aorta

摘要: 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 involved in effect on vitro model rat isolated thoracic aortic rings. (30 μM 10 mM) induced dose-dependent relaxation both endothelium-intact and endothelium-denuded rings with respective EC50 values 0.78 ± 0.08 1.91 0.21 mM. Endothelium removal or inhibition nitric oxide (NO) synthase N(ω)-nitro-L-arginine-methyl ester (L-NAME) significantly decreased did not abolish apocynin. By contrast, apocynin-induced was unchanged after incubation indomethacin charybdotoxin plus apamin. In aortas, reduced by glibenclamide 4-aminopyridine nor iberiotoxin. Ca(2+)-induced contraction inhibited intracellular Ca(2+) mobilization phenylephrine. Finally, acute intravenous injection led immediate transient hypotensive spontaneously hypertensive rats (SHR). conclusion, our demonstrated induces endothelium-independent relaxant effects involving activation KATP channels vascular smooth muscle cells endothelium-dependent mediated NO. These results should provide basis for caution when interpreting