Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Prostaglandins Other Lipid Mediat. 2021 Jun;154:106548. doi: 10.1016/j.prostaglandins.2021.106548. Epub 2021 Mar 19.
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.
我们之前曾报道过，20-HETE 或 CYP4A 的缺乏会损害大鼠的肌原性反应和脑血流 (CBF) 的自动调节。本研究表明，CYP4A 与血管平滑肌细胞 (VSMCs) 中的 α-平滑肌肌动蛋白 (α-SMA) 以及从 SD 大鼠分离的实质动脉 (PA) 周围的大多数周细胞共表达。用 20-HETE 合成抑制剂 HET0016 可降低脑 VSMCs 和周细胞的收缩能力，但用 20-HETE 类似物 WIT003 可恢复。同样，SD 大鼠大脑中动脉和 PA 的完整肌原性反应随着 HET0016 的增加而降低，并通过 WIT003 得以挽救。PA 的肌原性反应在 SS 中被消除，并在 SS.BN5 和 SS.Cyp4a1 大鼠中恢复。HET0016 增加了 SD 大鼠表面和深层皮质的 CBF，并损害了其自动调节。这些结果表明，20-HETE 对脑壁细胞收缩有直接影响，可能在控制脑血管功能中发挥重要作用。
