Studies on arginine-nitric oxide system in the regulation of thermogenic organ brown adipose tissue

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Significance of nitric oxide (NO) in the regulation of blood flow and thermogenesis in brown adipose tissue (BAT) was investigated in rat.The following findings were obtained. (1) NO synthase inhibitor L^<omega>-nitro-arginine methyl ester (L-NAME) suppressed the cold-induced increase in blood flow as well as tissue temperature. It was also confirmed that noradreanline-induced increase in these parameters was suppressed by L-NAME.(2) Isoproterenol increased BAT blood flow and temperature. However, phynylephrine increased BAT temperature, but did not affect blood flow. This effect was also suppressed by L-NAME.Isoproterenol plus phenylephrine increased BAT blood flow and temperature earlier than isoproterenol alone. CL316,243 increased BAT blood flow and temperature. These effects were also inhibited by L-NAME.The results suggest that BAT blood flow as well as thermogenesis is regulated mainly by beta-adrenoreceptors and partly by alpha_<1-> adrenoreceptor, and NO may be a common mediator for their regulations. (3) The chronic administration of L-NAME decreased BAT weight as well as DNA content and inhibited the cold-stimulated increase in BAT weight and DNA content. Chronic L-NAME administration inhibited noradreanline-stimulated increase in in vivo oxygen consumption (nonshivering thermogenic capacity) and decreased cold tolerance as estimated by the fall of colonic temperature in cold. (4) In vitro incubation of BAT with L-NAME suppressed the basal and noradreanline-stumulated increase in in vitro oxygen consumption. In vitro incubation of BAT with methylene blue, scavenger of NO and guanylate cyclase inhibitor, eliminated noradrenaline-stimulated in in vitro BAT oxygen consumption. (5) L-NAME inhibited an increase in blood flow through BAT induced by electrical stumulation of ventromedial nucleus of hypothalamus.These findings suggest that NO is involved in the regulation of not only blood flow, but also proliferation and thermogenesis of brown adipose tissue.