Effects of Early Post-Ischemic Reperfusion and tPA on Cerebrovascular Function and Nitrosative Stress in Female Rats

被引:27
作者
Ahnstedt, Hilda [1 ]
Sweet, Julie [1 ]
Cruden, Patrick [1 ]
Bishop, Nicole [1 ]
Cipolla, Marilyn J. [1 ,2 ]
机构
[1] Univ Vermont, Coll Med, Dept Neurol Sci, HSRF 416A,149 Beaumont Ave, Burlington, VT 05405 USA
[2] Univ Vermont, Coll Med, Dept Obstet Gynecol & Reprod Sci, HSRF 416A,149 Beaumont Ave, Burlington, VT 05405 USA
关键词
Cerebral ischemia; Reperfusion; Myogenic tone; Middle cerebral arteries; Parenchymal arterioles; 3-Nitrotyrosine; TISSUE-PLASMINOGEN ACTIVATOR; CEREBRAL-ARTERY OCCLUSION; SEX-BASED DIFFERENCES; MYOGENIC TONE; ISCHEMIC-STROKE; INTRAARTERIAL TREATMENT; PARENCHYMAL ARTERIOLES; LEUKOCYTE ACCUMULATION; THRESHOLD DURATION; BLOOD-FLOW;
D O I
10.1007/s12975-016-0468-4
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Stroke is a major health issue in women. Our previous studies in male rats showed decreased myogenic tone in middle cerebral arteries (MCAs) after ischemia and reperfusion (I/R), while tone in parenchymal arterioles (PAs) was increased. This vascular response may aggravate stroke damage in males by limiting reperfusion; however, the effect in females is not known. The current study investigated the effect of I/R and tissue plasminogen activator (tPA) on myogenic tone and reactivity of MCAs and PAs in female rats. Nitrosative stress by peroxynitrite and recruitment of inflammatory neutrophils to the microvasculature were also studied. Female rats were subjected to 2-h MCA filament occlusion (n = 16) or sham surgery (n = 17) and given tPA (1 mg/kg, i.v) or vehicle followed by 30-min reperfusion. Myogenic tone and reactivity were measured in isolated and pressurized MCAs and PAs from the same animals. Cerebrovascular F-actin, 3-nitrotyrosine (3-NT, peroxynitrite marker), and intravascular neutrophils were quantified. Myogenic tone and constriction to the nitric oxide synthase inhibitor N omega-nitro-L-arginine were decreased in MCAs but unchanged in PAs after I/R with no effect of tPA. F-actin and 3-NT expression were unaffected by I/R or tPA. Our study showed that MCAs from females, similar to what has been seen in males, are dilated after I/R and have decreased myogenic tone while tone in PAs was unchanged. Increased small vessel resistance may contribute to decreased reperfusion and worse outcome after stroke.
引用
收藏
页码:228 / 238
页数:11
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