Pal Soumiya, Bagchi Ashim K, Henry David S, Landes Reid D, Mu Shengyu, Rhee Sung W, Rusch Nancy J, Stolarz Amanda J
Department of Pharmaceutical Sciences, College of Pharmacy (S.P., A.K.B., A.J.S.), University of Arkansas for Medical Sciences, Little Rock, AR.
Department of Pharmacology and Toxicology, College of Medicine (D.S.H., S.M., S.W.R., N.J.R., A.J.S.), University of Arkansas for Medical Sciences, Little Rock, AR.
Hypertension. 2025 Jan;82(1):72-83. doi: 10.1161/HYPERTENSIONAHA.124.23194. Epub 2024 Nov 6.
Hypertension increases the risk of lymphedema in patients with comorbidities, but whether hypertension directly compromises lymph vessel (LV) function and lymph flow is unclear. We compared the contractions of mesenteric LVs ex vivo and lymph flow in vivo between normotensive and Ang II (angiotensin II)-induced hypertensive rats and explored the ionic basis of contractile patterns. Key studies were recapitulated in spontaneously hypertensive rats and control Wistar-Kyoto rats.
Video microscopy continuously recorded the diameters of cannulated rat mesenteric LVs, and high-speed optical imaging estimated mesenteric lymph flow in vivo. Jess capillary Western electrophoresis evaluated expression levels of ion channel proteins.
Isolated LVs from Ang II-induced hypertensive rats exhibited dysrhythmic contractions, whereas LVs from both Ang II-induced hypertensive rats and spontaneously hypertensive rats exhibited reduced diastolic diameters and cross-sectional flow. Mesenteric lymph flow in vivo was 2.9-fold lower in Ang II-induced hypertensive rats compared with normotensive rats. Surprisingly, the LVs from Ang II-induced hypertensive rats expressed fewer intact L-type Ca channel pore proteins and more modulatory cleaved C-terminal fragments. However, pharmacological block of voltage-gated K channels but not other K channel types in control LVs established the pattern of contractile dysfunction observed in hypertension. Jess capillary Western electrophoresis analysis confirmed a loss of Shaker-type K1.2 channels in LVs from hypertensive rats.
We provide initial evidence of lymphatic contractile dysfunction and compromised lymph flow in hypertensive rats, which may be caused by a loss of K1.2 channels in the lymphatic muscle cells.
高血压会增加合并症患者发生淋巴水肿的风险，但高血压是否直接损害淋巴管（LV）功能和淋巴流动尚不清楚。我们比较了正常血压大鼠和血管紧张素 II（Ang II）诱导的高血压大鼠离体肠系膜淋巴管的收缩情况以及体内淋巴流动情况，并探讨了收缩模式的离子基础。在自发性高血压大鼠和对照Wistar-Kyoto大鼠中重复了关键研究。
视频显微镜连续记录插管大鼠肠系膜淋巴管的直径，高速光学成像估计体内肠系膜淋巴流动情况。Jess毛细管免疫印迹法评估离子通道蛋白的表达水平。
来自Ang II诱导的高血压大鼠的离体淋巴管表现出节律紊乱的收缩，而来自Ang II诱导的高血压大鼠和自发性高血压大鼠的淋巴管均表现出舒张直径和横截面积减小。与正常血压大鼠相比，Ang II诱导的高血压大鼠体内肠系膜淋巴流动降低了2.9倍。令人惊讶的是，来自Ang II诱导的高血压大鼠的淋巴管表达的完整L型钙通道孔蛋白较少，而调节性裂解的C末端片段较多。然而，在对照淋巴管中对电压门控钾通道而非其他钾通道类型进行药理学阻断，确立了在高血压中观察到的收缩功能障碍模式。Jess毛细管免疫印迹分析证实高血压大鼠淋巴管中Shaker型K1.2通道缺失。
我们提供了高血压大鼠淋巴收缩功能障碍和淋巴流动受损的初步证据，这可能是由淋巴肌细胞中K1.2通道缺失所致。
