Martin C M, Beltran-Del-Rio A, Albrecht A, Lorenz R R, Joyner M J
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):H442-6. doi: 10.1152/ajpheart.1996.270.2.H442.
To determine whether local cholinergic mechanisms evoke nitric oxide (NO)-mediated flow-induced vasorelaxation, canine coronary artery rings without endothelium were suspended beneath an organ chamber that contained a stainless steel tube and a femoral artery segment with endothelium. The rings were superfused at a basal rate of 1 ml/min with physiological salt solution that was bubbled with 95% O2-5% CO2 and maintained at 37 degrees C. They were stretched to optimal length and contracted with prostaglandin F 2 alpha (2 x 10(-6) M). When flow through the stainless steel tube (direct superfusion) was increased from the basal rate of 1 to 4 ml/min, coronary force did not change. Superfusion of the rings (n = 8) with effluent from the femoral segment (endothelial superfusion) at 4 ml/min to study flow-induced vasodilation caused a 67.3 +/- 10.8% relaxation. Treatment of the segment with the NO synthase blocker NG-monomethyl-L-arginine (10(-4) M) eliminated the relaxation seen during endothelial superfusion (P < 0.05 vs. control). Application of atropine (10(-6) M) to additional femoral segments (n = 8) abolished the coronary relaxation observed during endothelial superfusion at 1 ml/ min, and the flow-induced relaxation observed at 4 ml/min was reduced from 64 +/- 8.3 to 27 +/- 5.6% (P < 0.05 vs. control). In studies on additional segments and rings (n = 6), the flow-induced relaxations at 4 ml/min of endothelial superfusion were blunted from 86 +/- 10 to 28 +/- 13% after the segments were treated with acetylcholinesterase (0.00028 U/min for 20 min). These data indicate that basal- and flow-induced release of NO from the vascular endothelium can be mediated by local cholinergic mechanisms. It is possible that flow causes acetylcholine release from certain endothelial cells, which stimulates NO release from these cells or from neighboring endothelial cells.
为了确定局部胆碱能机制是否能引发一氧化氮（NO）介导的血流诱导的血管舒张，将无内皮的犬冠状动脉环悬挂于一个器官腔室下方，该腔室包含一根不锈钢管和一段有内皮的股动脉段。这些血管环以1毫升/分钟的基础速率用生理盐溶液进行 superfused，该溶液用95% O₂ - 5% CO₂ 鼓泡并维持在37摄氏度。将它们拉伸至最佳长度，并用前列腺素F₂α（2×10⁻⁶ M）使其收缩。当通过不锈钢管的血流（直接superfusion）从基础速率1毫升/分钟增加到4毫升/分钟时，冠状动脉张力未发生变化。以4毫升/分钟的速率用来自股动脉段的流出液对血管环（n = 8）进行superfusion（内皮superfusion）以研究血流诱导的血管舒张，导致舒张67.3±10.8%。用NO合酶阻滞剂NG - 单甲基 - L - 精氨酸（10⁻⁴ M）处理该段血管消除了内皮superfusion期间出现的舒张（与对照组相比，P < 0.05）。对另外的股动脉段（n = 8）应用阿托品（10⁻⁶ M）消除了在1毫升/分钟内皮superfusion期间观察到的冠状动脉舒张，并且在4毫升/分钟时观察到的血流诱导的舒张从64±8.3%降低至27±5.6%（与对照组相比，P < 0.05）。在对另外的段和血管环（n = 6）的研究中，在用乙酰胆碱酯酶（0.00028 U/分钟，持续20分钟）处理段之后，在4毫升/分钟内皮superfusion时的血流诱导的舒张从86±10%减弱至28±13%。这些数据表明，血管内皮中基础和血流诱导的NO释放可由局部胆碱能机制介导。血流可能导致乙酰胆碱从某些内皮细胞释放，这刺激这些细胞或相邻内皮细胞释放NO。
