Xu B, Li J, Gao L, Ferro A
Cardiovascular Research Unit, Department of Medicine, Nanjing Railway Medical College, Nanjing 210009, China.
Br J Pharmacol. 2000 Mar;129(5):969-74. doi: 10.1038/sj.bjp.0703155.
Some studies suggest that beta-adrenoceptor-mediated vasorelaxation is in part mediated through nitric oxide (NO) release. We wished to determine the contribution of the L-arginine / NO system to vasodilatation in response to beta-adrenoceptor stimulation with isoprenaline or cyclic adenosine-3',5'-monophosphate (cyclic AMP) elevation with forskolin and dibutyryl cyclic AMP in vivo, using a rabbit femoral artery constant perfusion model. Baseline femoral artery pressure was similar in rabbits receiving isoprenaline, forskolin or dibutyryl cyclic AMP. Isoprenaline, forskolin and dibutyryl cyclic AMP each decreased femoral artery pressure in a dose-dependent manner. The doses (mol kg(-1)) of isoprenaline, forskolin and dibutyryl cyclic AMP which decreased pressure by 10% from baseline, expressed as a negative logarithm (-log ED(10)) were: 10.0+/-0.2, 9.5+/-0.1 and 4.9+/-0.1 respectively (P<0.0001 for each). Use of beta-adrenoceptor subtype-selective antagonists showed that the vascular response to isoprenaline was purely due to stimulation of the beta(2)-adrenoceptor subtype. Injection of 1 micromol kg(-1) N(G)-nitro-L-arginine methyl ester (L-NAME) did not alter baseline pressure. However, it abolished the pressure response to isoprenaline (P<0.0001), and significantly attenuated the pressure responses to forskolin and dibutyryl cyclic AMP: -log ED(10) values for forskolin and dibutyryl cyclic AMP, in the presence of L-NAME, were 7.9+/-0.1 and 3.5+/-0.3 respectively (P<0.0001 for each, as compared with values in the absence of L-NAME). These results indicate that beta(2)-adrenergic stimulation and cylic AMP elevation activate the L-arginine/NO system in rabbit femoral artery in vivo, and that NO generation contributes importantly to the changes in vascular tone induced by agents which modulate beta-adrenoceptors or cyclic AMP.
一些研究表明，β-肾上腺素受体介导的血管舒张部分是通过一氧化氮（NO）释放介导的。我们希望使用兔股动脉恒压灌注模型，在体内确定L-精氨酸/NO系统对异丙肾上腺素刺激β-肾上腺素受体或福斯可林和二丁酰环磷腺苷升高环磷腺苷（cAMP）所引起的血管舒张的作用。接受异丙肾上腺素、福斯可林或二丁酰环磷腺苷的兔子的股动脉基线压力相似。异丙肾上腺素、福斯可林和二丁酰环磷腺苷均以剂量依赖性方式降低股动脉压力。使压力从基线降低10%的异丙肾上腺素、福斯可林和二丁酰环磷腺苷的剂量（mol·kg⁻¹），以负对数（-log ED₁₀）表示分别为：10.0±0.2、9.5±0.1和4.9±0.1（每组P<0.0001）。使用β-肾上腺素受体亚型选择性拮抗剂表明，对异丙肾上腺素的血管反应完全是由于β₂-肾上腺素受体亚型的刺激。注射1 μmol·kg⁻¹的N⁺-硝基-L-精氨酸甲酯（L-NAME）不会改变基线压力。然而，它消除了对异丙肾上腺素的压力反应（P<0.0001），并显著减弱了对福斯可林和二丁酰环磷腺苷的压力反应：在存在L-NAME的情况下，福斯可林和二丁酰环磷腺苷的-log ED₁₀值分别为7.9±0.1和3.5±0.3（与不存在L-NAME时的值相比，每组P<0.0001）。这些结果表明，β₂-肾上腺素能刺激和cAMP升高在体内激活兔股动脉中的L-精氨酸/NO系统，并且NO生成对由调节β-肾上腺素受体或cAMP的药物引起的血管张力变化起重要作用。
