We previously reported that deficiency in 20-HETE or CYP4A impaired the myogenic response and autoregulation of cerebral blood flow (CBF) in rats. The present study demonstrated that CYP4A was coexpressed with alpha-smooth muscle actin (α-SMA) in vascular smooth muscle cells (VSMCs) and most pericytes along parenchymal arteries (PAs) isolated from SD rats. Cell contractile capabilities of cerebral VSMCs and pericytes were reduced with a 20-HETE synthesis inhibitor, HET0016, but restored with 20-HETE analog WIT003. Similarly, intact myogenic responses of the middle cerebral artery and PA of SD rats decreased with HET0016 and were rescued by WIT003. The myogenic response of the PA was abolished in SS and was restored in SS.BN5 and SS.Cyp4a1 rats. HET0016 enhanced CBF and impaired its autoregulation in the surface and deep cortex of SD rats. These results demonstrate that 20-HETE has a direct effect on cerebral mural cell contractility that may play an essential role in controlling cerebral vascular function.

我们之前报道过 20-HETE 或 CYP4A 的缺乏会损害大鼠的肌源性反应和脑血流 (CBF) 的自动调节。本研究表明，CYP4A 与从 SD 大鼠分离的血管平滑肌细胞 (VSMC) 和大多数沿实质动脉 (PA) 的周细胞中的 α-平滑肌肌动蛋白 (α-SMA) 共表达。使用 20-HETE 合成抑制剂 HET0016 可降低脑 VSMC 和周细胞的细胞收缩能力，但使用 20-HETE 类似物 WIT003 可恢复。同样，SD 大鼠大脑中动脉和 PA 的完整肌源性反应随着 HET0016 的降低而被 WIT003 挽救。PA 的肌源性反应在 SS 中被消除，在 SS.BN5 和 SS 中恢复。Cyp4a1老鼠。HET0016 增强 CBF 并损害其在 SD 大鼠表层和深层皮层的自动调节。这些结果表明，20-HETE 对脑壁细胞收缩具有直接影响，这可能在控制脑血管功能中起重要作用。