Rigsby Christine' S, Pollock David M, Dorrance Anne M
Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3000, USA.
Microvasc Res. 2007 May;73(3):198-205. doi: 10.1016/j.mvr.2006.12.001. Epub 2007 Jan 23.
Previous studies show that ischemic cerebral infarct size is related to cerebral vessel structure. Spironolactone, a mineralocorticoid receptor antagonist, decreases ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that chronic spironolactone treatment would improve cerebral artery structure in the SHRSP.
Six-week-old male SHRSP were treated with spironolactone (2.5 mg/day) for 6 weeks and were compared to untreated control SHRSP and normotensive Wistar Kyoto (WKY) rats. Using a pressurized arteriograph, structural measurements of the middle cerebral artery (MCA) were taken under passive (calcium-free), zero-flow conditions. Myogenic tone was calculated from active and passive measurements taken at 75 and 125 mmHg. Mean arterial pressure was measured using radiotelemetry.
Myogenic tone was increased only at 75 mmHg in the spironolactone-treated SHRSP compared to control rats. The MCA lumen and outer diameters were increased in the spironolactone-treated SHRSP compared to control SHRSP, but were not different from WKY rats, indicating a decrease in vascular remodeling. There was no effect of spironolactone on blood pressure, suggesting that this is a blood pressure-independent effect.
Increased myogenic tone and lumen diameter in the spironolactone-treated SHRSP may be responsible for the protective role of spironolactone in ischemic stroke.
既往研究表明,缺血性脑梗死面积与脑血管结构有关。螺内酯是一种盐皮质激素受体拮抗剂,可减小雄性自发性高血压易卒中型大鼠(SHRSP)的缺血性脑梗死面积。因此,我们推测长期使用螺内酯治疗可改善SHRSP的脑动脉结构。
六周龄雄性SHRSP接受螺内酯(2.5毫克/天)治疗6周,并与未治疗的对照SHRSP和正常血压的Wistar Kyoto(WKY)大鼠进行比较。使用加压动脉造影仪,在被动(无钙)、零流量条件下对大脑中动脉(MCA)进行结构测量。根据在75和125 mmHg下进行的主动和被动测量计算肌源性张力。使用无线电遥测法测量平均动脉压。
与对照大鼠相比,螺内酯治疗的SHRSP仅在75 mmHg时肌源性张力增加。与对照SHRSP相比,螺内酯治疗的SHRSP的MCA管腔和外径增加,但与WKY大鼠无差异,表明血管重塑减少。螺内酯对血压无影响,提示这是一种不依赖血压的效应。
螺内酯治疗的SHRSP中肌源性张力和管腔直径增加可能是螺内酯在缺血性卒中中发挥保护作用的原因。