Liu Y, Liu T, McCarron R M, Spatz M, Feuerstein G, Hallenbeck J M, Sirén A L
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Am J Physiol. 1996 Jun;270(6 Pt 2):H2125-31. doi: 10.1152/ajpheart.1996.270.6.H2125.
We have proposed that an interaction between perivascular macrophages and endothelium via cytokines could underlie the increased risk of stroke in hypertension. Therefore, the activation of monocytes, the endothelial expression of intercellular adhesion molecule-1 (ICAM-1), and the numbers of monocytes/macrophages in carotid arteries, as well as the cytokine production in carotid tissue, of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto and Sprague-Dawley rats were studied. The total number of blood monocytes (890 +/- 153 cells/mm3, n = 10) and the number of activated (nitro blue tetrazolium-positive) monocytes (220 +/- 51 cells/mm3, n = 10) were significantly greater (P < 0.05) in SHR than in WKY rats (440 +/- 81 and 40 +/- 16 cells/mm3, respectively, n = 10). Patchy endothelial expression of ICAM-1 was found in 77 +/- 9% of carotid sections from stroke-prone SHR (SHR-SP, n = 5) and in 75 +/- 7% of the sections from SHR (n = 7) but in none of the sections from the two normotensive rat strains (n = 7). The number of endothelium-attached monocytes/macrophages per millimeter of internal elastic lamina was significantly greater in SHR-SP than in SHR [5.1 +/- 0.7 (n = 4) and 3.3 +/- 0.3 (n = 6), P < 0.05], whereas no monocytes were found around the endothelium in either of the normotensive rat strains (n = 7 in each group). Incubation of the carotid arteries with lipopolysaccharide (30-300 ng/ml) induced a concentration-dependent expression of mRNAs for interleukin-1 beta and release of tumor necrosis factor-alpha to a significantly greater degree in the SHR than in the Wistar-Kyoto rats. The results demonstrate that hypertension is associated with activation of monocytes and endothelium and an increased endothelial adhesion and subendothelial accumulation of monocytes/macrophages and with an increased vascular capacity to produce cytokines.
我们曾提出，血管周围巨噬细胞与内皮细胞之间通过细胞因子进行的相互作用可能是高血压患者中风风险增加的潜在原因。因此，我们研究了自发性高血压大鼠（SHR）以及血压正常的Wistar-Kyoto大鼠和Sprague-Dawley大鼠的单核细胞活化、细胞间黏附分子-1（ICAM-1）的内皮表达、颈动脉中单核细胞/巨噬细胞的数量以及颈动脉组织中的细胞因子产生情况。SHR血液中单核细胞的总数（890±153个细胞/mm³，n = 10）和活化（硝基蓝四氮唑阳性）单核细胞的数量（220±51个细胞/mm³，n = 10）显著高于WKY大鼠（分别为440±81和40±16个细胞/mm³，n = 10）（P < 0.05）。在易中风SHR（SHR-SP，n = 5）的77±9%的颈动脉切片以及SHR（n = 7）的75±7%的切片中发现了ICAM-1的斑片状内皮表达，但在两种血压正常大鼠品系的切片中均未发现（n = 7）。每毫米内弹性膜上附着在内皮上的单核细胞/巨噬细胞数量，SHR-SP显著多于SHR [分别为5.1±0.7（n = 4）和3.3±0.3（n = 6），P < 0.05]，而在两种血压正常大鼠品系中，在内皮周围均未发现单核细胞（每组n = 7）。用脂多糖（30 - 300 ng/ml）孵育颈动脉，诱导白细胞介素-1β mRNA的浓度依赖性表达以及肿瘤坏死因子-α的释放，SHR的诱导程度显著高于Wistar-Kyoto大鼠。结果表明，高血压与单核细胞和内皮细胞的活化、单核细胞/巨噬细胞在内皮的黏附增加及内皮下积聚增加以及血管产生细胞因子的能力增强有关。
