Uchida Y, Tsukahara F, Irie K, Nomoto T, Muraki T
Department of Pharmacology, Tokyo Women's Medical College, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):188-93. doi: 10.1007/BF00169836.
To evaluate whether the L-arginine-nitric oxide (NO) pathway is involved in the regulation of regional blood flow to brown adipose tissue (BAT), the effects of two specific NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), on the blood flow to interscapular brown adipose tissue (IBAT) were studied in urethane-anesthetized rats. Regional blood flow in IBAT was measured with laser-Doppler flowmetry. An intravenous injection of L-NAME and L-NMMA, but not of either D-enantiomer, caused a transient and dose-dependent increase in IBAT blood flow. Dose-response curves for these NO synthase inhibitors showed that L-NAME was more potent than L-NMMA in increasing IBAT blood flow. We also observed a concomitant pressor effect accompanied by a slight decrease in heart rate following intravenous injection of L-NAME and L-NMMA. An elevation of IBAT blood flow and blood pressure induced by both L-NAME and L-NMMA was reversed by L-arginine in an enantiomerically specific manner. The increase in IBAT blood flow induced by NO synthase inhibitors was of shorter duration and less sensitive to L-arginine than the increase in blood pressure. Our results show that the IBAT blood flow is increased by inhibition of NO synthase and that the response of IBAT vasculature to NO synthase inhibitors is different from that of the resistance vessels which regulate blood pressure. The involvement of L-arginine-NO pathways in modulating microcirculation in IBAT is suggested.
为了评估L-精氨酸-一氧化氮(NO)途径是否参与调节棕色脂肪组织(BAT)的局部血流,我们在氨基甲酸乙酯麻醉的大鼠中研究了两种特异性NO合酶抑制剂,NG-硝基-L-精氨酸甲酯(L-NAME)和NG-单甲基-L-精氨酸(L-NMMA)对肩胛间棕色脂肪组织(IBAT)血流的影响。用激光多普勒血流仪测量IBAT的局部血流。静脉注射L-NAME和L-NMMA可引起IBAT血流短暂且剂量依赖性增加,而注射两种药物的D-对映体则无此作用。这些NO合酶抑制剂的剂量反应曲线表明,在增加IBAT血流方面,L-NAME比L-NMMA更有效。我们还观察到,静脉注射L-NAME和L-NMMA后,伴随有轻微的心率下降,同时出现升压效应。L-精氨酸以对映体特异性方式逆转了L-NAME和L-NMMA引起的IBAT血流增加和血压升高。与血压升高相比,NO合酶抑制剂引起的IBAT血流增加持续时间更短,对L-精氨酸的敏感性更低。我们的结果表明,抑制NO合酶可增加IBAT血流,且IBAT血管系统对NO合酶抑制剂的反应与调节血压的阻力血管不同。这提示L-精氨酸-NO途径参与调节IBAT的微循环。