Rigsby Christiné S, Burch Ashley E, Ogbi Safia, Pollock David M, Dorrance Anne M
Dept. of Physiology, Medical College of Georgia, 1120 15th St. (CA2091) Augusta, Georgia 30912-3000, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1754-63. doi: 10.1152/ajpregu.00145.2007. Epub 2007 Aug 1.
Data from the Framingham Heart Study suggest that women may be more sensitive to the deleterious cardiovascular remodeling effects of aldosterone. Previous studies from our laboratory have shown that chronic treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist, decreases ischemic cerebral infarct size and prevents remodeling of the middle cerebral artery (MCA) in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that MR antagonism would reduce ischemic infarct size and prevent MCA remodeling in female SHRSP. Six-week-old female SHRSP were treated for 6 wk with spironolactone (25 or 50 mg.kg(-1).day(-1)) or eplerenone (100 mg.kg(-1).day(-1)) and compared with untreated controls. At 12 wk, cerebral ischemia was induced for 18 h using the intraluminal suture occlusion technique, or the MCA was isolated for analysis of passive structure using a pressurized arteriograph. MR antagonism had no effect on infarct size or passive MCA structure in female SHRSP. To study the potential effects of estrogen, the above experiments were repeated in bilaterally ovariectomized (OVX) female SHRSP treated with spironolactone (25 mg.kg(-1).day(-1)). Infarct size and vessel structure in OVX SHRSP were not different from control SHRSP. Spironolactone had no effect on infarct size in OVX SHRSP. However, MCA lumen and outer diameters were increased in spironolactone-treated OVX SHRSP, suggesting an effect of estrogen. Cerebral artery MR expression, assessed by Western blotting, was increased in female, compared with male, SHRSP. These studies highlight an apparent sexual dimorphism of MR expression and activity in the cerebral vasculature from hypertensive rats.
弗明汉心脏研究的数据表明，女性可能对醛固酮有害的心血管重塑作用更为敏感。我们实验室之前的研究表明，用盐皮质激素受体（MR）拮抗剂螺内酯进行长期治疗，可减小雄性自发性高血压易中风大鼠（SHRSP）的缺血性脑梗死体积，并防止大脑中动脉（MCA）重塑。因此，我们推测MR拮抗作用会减小雌性SHRSP的缺血性梗死体积并防止MCA重塑。六周龄雌性SHRSP用螺内酯（25或50mg·kg⁻¹·d⁻¹）或依普利酮（100mg·kg⁻¹·d⁻¹）治疗6周，并与未治疗的对照组进行比较。在12周时，采用腔内缝线闭塞技术诱导脑缺血18小时，或分离MCA以使用加压动脉造影仪分析其被动结构。MR拮抗作用对雌性SHRSP的梗死体积或MCA被动结构没有影响。为了研究雌激素的潜在作用，在用螺内酯（25mg·kg⁻¹·d⁻¹）治疗的双侧卵巢切除（OVX）雌性SHRSP中重复上述实验。OVX SHRSP的梗死体积和血管结构与对照SHRSP没有差异。螺内酯对OVX SHRSP的梗死体积没有影响。然而，在螺内酯治疗的OVX SHRSP中，MCA管腔和外径增加，提示雌激素的作用。通过蛋白质印迹法评估，与雄性SHRSP相比，雌性SHRSP脑动脉MR表达增加。这些研究突出了高血压大鼠脑血管中MR表达和活性明显的性别差异。
