Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA.
Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA; Department of Pharmacology, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA.
Microvasc Res. 2018 Sep;119:64-72. doi: 10.1016/j.mvr.2018.04.007. Epub 2018 Apr 26.
Preeclampsia (PE), a dangerous hypertensive complication of pregnancy, is associated with widespread maternal vascular dysfunction. However, the effect of PE on the cerebral vasculature that can lead to stroke and cognitive decline is not well understood. We hypothesized that function of cortical parenchymal arterioles (PAs) would be impaired during PE. Using a high cholesterol diet to induce experimental PE in rats (ePE), we studied the function and structure of isolated and pressurized PAs supplying frontoparietal white matter (WM) tracts and cortex and compared to normal pregnant (Preg) and nonpregnant (Nonpreg) Sprague Dawley rats (n = 8/group). Myogenic reactivity and tone were similar between groups; however, constriction to intermediate-conductance calcium-activated potassium (IK) channel inhibition was diminished and dilation to inward-rectifying K (K) channel activation was impaired in PAs from ePE rats, suggesting altered ion channel function. Conducted vasodilation was significantly delayed in response to 12 mM KCl, but not 10 μM adenosine, in PAs from ePE rats versus Preg and Nonpreg rats (940 ± 300 ms vs. 70 ± 50 ms and 370 ± 90 ms; p < 0.05). Overall, dysfunction of PAs supplying frontoparietal WM and gray matter was present in ePE. If persistent these changes could potentiate neuronal injury that over time could contribute to WM lesions and early-onset cognitive decline.
子痫前期 (PE) 是一种严重的妊娠高血压并发症，与广泛的母体血管功能障碍有关。然而，PE 对脑血管的影响，从而导致中风和认知能力下降的机制尚不清楚。我们假设在 PE 期间皮质实质小动脉 (PA) 的功能会受到损害。我们使用高胆固醇饮食在大鼠中诱导实验性 PE (ePE)，研究了供应额顶叶白质 (WM) 束和皮质的分离和加压 PA 的功能和结构，并与正常妊娠 (Preg) 和非妊娠 (Nonpreg) Sprague Dawley 大鼠进行了比较 (n=8/组)。各组之间肌源性反应性和张力相似；然而，ePE 大鼠的 PA 对中等电导钙激活钾 (IK) 通道抑制的收缩反应减弱，对内流整流钾 (K) 通道激活的扩张反应受损，提示离子通道功能改变。与 Preg 和 Nonpreg 大鼠相比，ePE 大鼠的 PA 对 12 mM KCl 的传导性血管舒张反应明显延迟，但对 10 μM 腺苷没有延迟 (940±300 ms 与 70±50 ms 和 370±90 ms；p<0.05)。总的来说，供应额顶叶 WM 和灰质的 PA 功能障碍存在于 ePE 中。如果这些变化持续存在，可能会加剧神经元损伤，随着时间的推移，这可能会导致 WM 病变和早发性认知能力下降。
