Wilson S K
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Circ Res. 1990 Mar;66(3):722-34. doi: 10.1161/01.res.66.3.722.
Severe experimental hypertension is associated with vascular hyperpermeability and cellular damage in small arteries and arterioles in rats. Oxygen-derived free radical production is also associated with increased vascular permeability and cellular injury in a variety of conditions, including ischemia-reperfusion and inflammation. To determine if free radicals play a role in the pathogenesis of hypertensive vascular disease, the free radical scavengers superoxide dismutase (SOD), catalase, SOD and catalase, and dimethyl sulfoxide (DMSO) were given to rats made acutely hypertensive with angiotensin II infusions. Untreated hypertensive and normotensive control animals were used for comparison. The effects of scavenger treatment were assessed by in vivo observations of intestinal small arteries by use of stereomicroscopy and videotape and light and transmission electron microscopy to identify and quantitate vascular lesions, and tracer particle injections to determine permeability changes. In vivo observations revealed that scavenger treatment did not alter vascular constriction patterns, vessel caliber, or blood pressures. Electron microscopy of arteries from untreated hypertensive rats showed more severe and more extensive endothelial and smooth muscle lesions, increased tracer particle penetration, and greater fibrin deposition than that found in scavenger-treated hypertensive groups. Quantitation of vascular lesions showed approximately equal reductions in smooth muscle necrosis (p less than 0.01) and fibrin deposition (p less than 0.05) in arteries from each of the scavenger-treated hypertensive groups. The results indicate that the free radical scavengers SOD, catalase, SOD-catalase, and DMSO inhibit (but do not prevent) vascular hyperpermeability and cellular damage during acute, angiotensin II--induced hypertension. These findings suggest that free radicals play a role in the pathogenesis of hypertensive vascular disease, probably by exacerbating the vascular changes initially triggered by an acute elevation in blood pressure.
严重的实验性高血压与大鼠小动脉和微动脉的血管通透性增加及细胞损伤有关。在包括缺血再灌注和炎症在内的多种情况下，氧衍生的自由基生成也与血管通透性增加和细胞损伤有关。为了确定自由基是否在高血压血管疾病的发病机制中起作用，将自由基清除剂超氧化物歧化酶（SOD）、过氧化氢酶、SOD和过氧化氢酶以及二甲基亚砜（DMSO）给予通过输注血管紧张素II而急性高血压的大鼠。未治疗的高血压和正常血压对照动物用于比较。通过体视显微镜和录像以及光镜和透射电子显微镜对肠小动脉进行体内观察，以识别和定量血管病变，并通过注射示踪颗粒来确定通透性变化，从而评估清除剂治疗的效果。体内观察显示，清除剂治疗并未改变血管收缩模式、血管口径或血压。未治疗的高血压大鼠动脉的电子显微镜检查显示，与清除剂治疗的高血压组相比，内皮和平滑肌病变更严重、更广泛，示踪颗粒穿透增加，纤维蛋白沉积更多。血管病变的定量分析表明，每个清除剂治疗的高血压组动脉中的平滑肌坏死（p小于0.01）和纤维蛋白沉积（p小于0.05）均有近似程度的减少。结果表明，自由基清除剂SOD、过氧化氢酶、SOD-过氧化氢酶和DMSO在急性血管紧张素II诱导的高血压期间抑制（但不能预防）血管通透性增加和细胞损伤。这些发现表明，自由基在高血压血管疾病的发病机制中起作用，可能是通过加剧最初由血压急性升高引发的血管变化来实现的。
