Dinerman J L, Lawson D L, Mehta J L
Department of Medicine, University of Florida College of Medicine, Gainesville.
Am J Physiol. 1991 Mar;260(3 Pt 2):H698-701. doi: 10.1152/ajpheart.1991.260.3.H698.
To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.
为评估内皮在硝酸甘油（NTG）介导的血管舒张中的作用，将有完整内皮和无完整内皮的肾上腺素预收缩大鼠胸主动脉节段暴露于NTG（10⁻¹⁰至10⁻⁵M）。有完整内皮（endo+，n = 15）和去内皮（endo-，n = 9）的主动脉节段均表现出典型的NTG诱导的舒张。然而，NTG的平均有效浓度endo-节段低于endo+节段（P < 0.001）。为确定该现象是否与内皮产生一氧化氮（NO）有关，对六个endo+节段用NO产生抑制剂NG-甲基-L-精氨酸（L-NMMA）进行处理。这些endo+节段对NTG的反应比未处理的endo+节段表现出更大的舒张（P < 0.001）。鸟苷酸环化酶激活抑制剂氧合血红蛋白极大地减弱了所有主动脉节段的NTG介导的舒张。为确定endo-节段增强的NTG介导的舒张是否是鸟苷3',5'-环磷酸依赖性血管舒张剂NTG所特有的，将其他endo+和endo-节段暴露于腺苷3',5'-环磷酸依赖性血管舒张剂罂粟碱（10⁻⁸至10⁻⁴M），endo+和endo-节段之间的半数有效浓度（EC50）未发现差异。因此，内皮减弱了NTG介导的血管舒张，并且用L-NMMA抑制内皮NO产生可消除这种减弱作用。这些观察结果表明内皮是NTG对血管平滑肌舒张作用的动态调节剂。这种调节似乎是由内皮NO与NTG之间的竞争性相互作用引起的。
