Banda M A, Lefer D J, Granger D N
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Am J Physiol. 1997 Dec;273(6):H2721-5. doi: 10.1152/ajpheart.1997.273.6.H2721.
Previous studies utilizing monoclonal antibodies directed against specific leukocyte-endothelial cell adhesion proteins have suggested that neutrophils mediate endothelial cell injury in a number of vascular beds after ischemia-reperfusion (I/R). In the present study, we investigated superior mesenteric artery (SMA) vascular reactivity to acetylcholine (ACh) and sodium nitroprusside (SNP) after occlusion and reperfusion in wild-type (C57BL/6) mice and in gene-targeted mice that are deficient in either CD11/CD18, intercellular adhesion molecule 1 (ICAM-1), or P-selectin. All mice were 4 wk of age, and the SMA was occluded for 45 min and then reperfused for 45 min. Segments of SMA were isolated and suspended in organ chambers and contracted with phenylephrine (10(-5) M), and the maximal vasorelaxation to ACh (10(-6) M) and SNP (10(-6) M) was measured. SMA from sham-operated C57BL/6 mice relaxed 83.5 +/- 3.3% to ACh and 91.7 +/- 3.4% to SNP. In contrast, segments of SMA from C57BL/6 mice subjected to I/R demonstrated a marked impairment in vasorelaxation to ACh (51.3 +/- 4.7%, P < 0.01 vs. sham) without any impairment in the vasoreactivity to SNP (86.1 +/- 5.5%). In CD11/CD18-deficient mice, SMA reactivity to ACh (84.7 +/- 2.3%) and SNP (91.2 +/- 2.8%) was unaffected by I/R. Similarly, SMA rings from ICAM-1-deficient mice exhibited normal vasorelaxation to ACh and SNP with maximal vasorelaxation of 83.1 +/- 2.9 and 87.4 +/- 3.0%, respectively. We also observed profound preservation of endothelium-dependent vasorelaxation after I/R in P-selectin-deficient mice. These findings indicate that leukocyte-endothelial cell adhesion molecule deficiency is associated with the preservation of endothelium-dependent vascular responses after I/R.
以往利用针对特定白细胞 - 内皮细胞黏附蛋白的单克隆抗体进行的研究表明，在缺血再灌注（I/R）后，中性粒细胞在多个血管床介导内皮细胞损伤。在本研究中，我们调查了野生型（C57BL/6）小鼠以及缺乏CD11/CD18、细胞间黏附分子1（ICAM - 1）或P - 选择素的基因靶向小鼠在肠系膜上动脉（SMA）闭塞和再灌注后对乙酰胆碱（ACh）和硝普钠（SNP）的血管反应性。所有小鼠均为4周龄，SMA闭塞45分钟，然后再灌注45分钟。分离SMA节段并悬浮于器官浴槽中并用去氧肾上腺素（10⁻⁵ M）使其收缩，然后测量对ACh（10⁻⁶ M）和SNP（10⁻⁶ M）的最大血管舒张。假手术的C57BL/6小鼠的SMA对ACh舒张83.5±3.3%，对SNP舒张91.7±3.4%。相比之下，经历I/R的C57BL/6小鼠的SMA节段对ACh的血管舒张明显受损（51.3±4.7%，与假手术组相比P < 0.01），而对SNP的血管反应性无任何受损（86.1±5.5%）。在缺乏CD11/CD18的小鼠中，SMA对ACh（84.7±2.3%）和SNP（91.2±2.8%）的反应性不受I/R影响。同样，来自缺乏ICAM - 1的小鼠的SMA环对ACh和SNP表现出正常的血管舒张，最大血管舒张分别为83.1±2.9%和87.4±3.0%。我们还观察到在缺乏P - 选择素的小鼠中，I/R后内皮依赖性血管舒张得到显著保留。这些发现表明，白细胞 - 内皮细胞黏附分子缺乏与I/R后内皮依赖性血管反应的保留有关。
