Chrissobolis Sophocles, Sobey Christopher G
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Stroke. 2004 Mar;35(3):747-52. doi: 10.1161/01.STR.0000116867.28589.3A. Epub 2004 Feb 5.
It is not known whether cerebral vasoprotective mechanisms in females include increased function of arterial K+ channels. We hypothesized that vasodilator responses mediated by activation of inwardly rectifying K+ (K(IR)) channels are greater in cerebral arteries of female versus male rats and that this is due to the effects of estrogen.
Changes in basilar artery diameter were measured with a cranial window preparation in anesthetized Sprague-Dawley rats.
K+ (5 and 10 mmol/L) caused greater vasodilatation in females (percent maximum, 21+/-3% and 58+/-7%, respectively) versus males (11+/-1% and 37+/-4%, respectively; P<0.05). In contrast, vasodilator responses to aprikalim (1 and 3 micromol/L) or acetylcholine (ACh, 1 and 10 micromol/L) did not differ between the genders. The selective K(IR) channel inhibitor barium ion (30 micromol/L) decreased basilar artery diameter in males but not females (-7+/-1% versus -2+/-1%, P<0.05) and selectively inhibited K+-induced vasodilatation by approximately 50% in both groups. Ovariectomy of female rats resulted in smaller vasodilator effects of K+, and chronic treatment of these rats with 17beta-estradiol (0.01 mg/kg per day for 7 days) normalized K+-induced vasodilatation. Furthermore, the selective M2 muscarinic ACh receptor antagonist methoctramine (1 micromol/L) increased responses to K+ in males to levels equivalent to responses in females but had no effect on responses to K+ in females.
K+ is a more powerful vasodilator in the female versus male cerebral circulation. This difference is estrogen dependent and could be due to a lack of M2 muscarinic ACh receptor-induced inhibition of K(IR) channel activation by K+ in female cerebral arteries.
尚不清楚女性的脑血管保护机制是否包括动脉钾通道功能增强。我们假设，内向整流钾（K(IR)）通道激活介导的血管舒张反应在雌性大鼠脑动脉中比雄性大鼠更强，且这是雌激素作用的结果。
在麻醉的Sprague-Dawley大鼠中，用颅窗制备法测量基底动脉直径变化。
与雄性大鼠（分别为11±1%和37±4%）相比，钾离子（5和10 mmol/L）在雌性大鼠中引起更大的血管舒张（最大百分比分别为21±3%和58±7%；P<0.05）。相比之下，对阿普卡林（1和3 μmol/L）或乙酰胆碱（ACh，1和10 μmol/L）的血管舒张反应在两性之间没有差异。选择性K(IR)通道抑制剂钡离子（30 μmol/L）使雄性大鼠基底动脉直径减小，但对雌性大鼠无此作用（分别为-7±1%和-2±1%，P<0.05），并在两组中选择性抑制钾离子诱导的血管舒张约50%。雌性大鼠卵巢切除导致钾离子的血管舒张作用减弱，用17β-雌二醇（每天0.01 mg/kg，共7天）对这些大鼠进行慢性治疗可使钾离子诱导的血管舒张恢复正常。此外，选择性M2毒蕈碱型乙酰胆碱受体拮抗剂甲硫氧胺（1 μmol/L）使雄性大鼠对钾离子的反应增加到与雌性大鼠反应相当的水平，但对雌性大鼠对钾离子的反应无影响。
在雌性与雄性脑循环中，钾离子是一种更强效的血管舒张剂。这种差异依赖于雌激素，可能是由于雌性脑动脉中缺乏M2毒蕈碱型乙酰胆碱受体诱导的钾离子对K(IR)通道激活的抑制作用。
