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

本文研究了一氧化氮（NO）对大鼠棕色脂肪组织（BAT）血流量和产热的调节作用。(1)NO合成酶抑制剂L^<omega>-硝基精氨酸甲酯（L-NAME）抑制冷诱导的血流量增加以及组织温度。也证实去甲肾上腺素诱导的这些参数的增加被L-NAME抑制。(2)异丙肾上腺素增加BAT血流量和温度。然而，Phynylephine增加BAT温度，但不影响血流量。异丙肾上腺素加苯肾上腺素使BAT血流量和体温增加的时间早于单用异丙肾上腺素。CL 316，243增加BAT血流量和温度。结果表明，BAT的血流量和产热主要受β受体的调节，部分受α受体的调节<1->，NO可能是它们调节的共同介质。(3)长期给予L-NAME降低BAT重量和DNA含量，并抑制冷刺激的BAT重量和DNA含量的增加。慢性L-NAME给药抑制去甲肾上腺素刺激的增加体内耗氧量（非颤抖性产热能力），并降低冷耐受性的结肠温度下降的估计在寒冷。(4)BAT与L-NAME的体外孵育抑制了基础和去甲肾上腺素刺激的体外耗氧量增加。在体外孵育的BAT与亚甲蓝，清除剂NO和鸟苷酸环化酶抑制剂，消除去甲肾上腺素刺激的体外BAT耗氧量。(5)L-NAME可抑制电刺激下丘脑腹内侧核引起的BAT血流量增加，提示NO不仅参与血流量的调节，而且参与棕色脂肪组织的增殖和产热。

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.