Nicotinamide and its metaboliteN-methylnicotinamide increase skin vascular permeability in rats

Abstract

It has been suggested that topically applied nicotinamide and its metabolite N-methylnicotinamide (NMN(+)) might be useful agents for treatment of dermatological disorders such as acne vulgaris and rosacea. This study aimed to find out if the mechanism of these therapeutic effects depends on their vascular effects, by investigating if nicotinamide and NMN(+) are able to influence vascular permeability of the vessels in the skin on the back of Wistar rats. A dose-dependent increase in vascular permeability was seen in rats treated intradermally with nicotinamide and NMN(+). Interestingly, a significantly stronger effect of NMN(+) compared with nicotinamide was evident. Increased vascular permeability in rats treated with 0.5% NMN(+) ointment was seen. Moreover, indomethacin, a cyclo-oxygenase 1 and 2 inhibitor and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, reduced the observed effects of nicotinamide and NMN(+). This study provides direct in vivo evidence that nicotinamide and its metabolite NMN(+) increase skin vascular permeability in rats by a mechanism that may involve NO and prostaglandins.