Soumiya Pal, Ashim K Bagchi, David S Henry, Reid D Landes, Shengyu Mu, Sung W Rhee, Nancy J Rusch, Amanda J Stolarz
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Jess capillary Western electrophoresis evaluated expression levels of ion channel proteins.</p><p><strong>Results: </strong>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<sup>2+</sup> channel pore proteins and more modulatory cleaved C-terminal fragments. However, pharmacological block of voltage-gated K<sup>+</sup> channels but not other K<sup>+</sup> 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 K<sub>V</sub>1.2 channels in LVs from hypertensive rats.</p><p><strong>Conclusions: </strong>We provide initial evidence of lymphatic contractile dysfunction and compromised lymph flow in hypertensive rats, which may be caused by a loss of K<sub>V</sub>1.2 channels in the lymphatic muscle cells.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"72-83"},"PeriodicalIF":6.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rhythmic Contractions of Lymph Vessels and Lymph Flow Are Disrupted in Hypertensive Rats.\",\"authors\":\"Soumiya Pal, Ashim K Bagchi, David S Henry, Reid D Landes, Shengyu Mu, Sung W Rhee, Nancy J Rusch, Amanda J Stolarz\",\"doi\":\"10.1161/HYPERTENSIONAHA.124.23194\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hypertension increases the risk of lymphedema in patients with comorbidities, but whether hypertension directly compromises lymph vessel (LV) function and lymph flow is unclear. 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引用次数: 0
摘要
背景:高血压会增加合并症患者发生淋巴水肿的风险,但高血压是否会直接损害淋巴管(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)诱导的高血压大鼠肠系膜左心室的体外收缩和体内淋巴流动,并探索了收缩模式的离子基础。主要研究在自发性高血压大鼠和对照组 Wistar-Kyoto 大鼠中进行了再现:视频显微镜连续记录插管大鼠肠系膜左心室的直径,高速光学成像估算体内肠系膜淋巴流量。Jess 毛细管 Western 电泳评估了离子通道蛋白的表达水平:结果:血管紧张素Ⅱ诱导的高血压大鼠离体左心室表现出节律失常收缩,而血管紧张素Ⅱ诱导的高血压大鼠和自发性高血压大鼠的左心室均表现出舒张期直径和横截面流量减小。Ang II 诱导的高血压大鼠体内肠系膜淋巴流量是正常血压大鼠的 2.9 倍。令人惊讶的是,血管紧张素 II 诱导的高血压大鼠左心室表达的完整 L 型 Ca2+ 通道孔蛋白较少,而表达的调节性裂解 C 端片段较多。然而,药理阻断电压门控 K+ 通道而非对照左心室中的其他 K+ 通道类型,可确定高血压中观察到的收缩功能障碍模式。Jess毛细血管Western电泳分析证实了高血压大鼠左心室中Shaker型KV1.2通道的缺失: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,这可能是淋巴肌细胞中 KV1.2 通道缺失造成的。
Rhythmic Contractions of Lymph Vessels and Lymph Flow Are Disrupted in Hypertensive Rats.
Background: 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.
Methods: 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.
Results: 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 Ca2+ 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 KV1.2 channels in LVs from hypertensive rats.
Conclusions: We provide initial evidence of lymphatic contractile dysfunction and compromised lymph flow in hypertensive rats, which may be caused by a loss of KV1.2 channels in the lymphatic muscle cells.
期刊介绍:
Hypertension presents top-tier articles on high blood pressure in each monthly release. These articles delve into basic science, clinical treatment, and prevention of hypertension and associated cardiovascular, metabolic, and renal conditions. Renowned for their lasting significance, these papers contribute to advancing our understanding and management of hypertension-related issues.