Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy
Yan Feng1
Ying Li2
Xinling Yang1
Limin Han3
Luning Wang1
Shan Gao1
Ruixue Yin1
Xue Wang1
Jiayang Li1
Meiming Liu1
Baiyan Li1
1.Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Medicine Research,Ministry of Education),College of Pharmacy,Harbin Medical University,Harbin 150081,China2.Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Medicine Research,Ministry of Education),College of Pharmacy,Harbin Medical University,Harbin 150081,China;Department of Pharmacy,PLA Rocket Force Characteristic Medical Center,Beijing 100088,China3.Department of Pharmacy,the First affiliated Hospital of Harbin Medical University,Harbin 150010,China
摘要：Objective: Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor (VEGF) that may cause cardiovascular toxicity, such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway. The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors (VEGFRs) expressed in the baroreflex afferent pathway in autonomic control of blood pressure (BP) regulation. Methods: The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia (NG) and nucleus of tractus solitary (NTS) using immunostaining and molecular approaches. The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions. Results: Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats. Microinjection of VEGF directly into the NG reduced the mean blood pressure (MBP) dose-dependently, which was less dramatic in renovascular hypertension (RVH) rats, suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions. Notably, this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2, which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension. Conclusion: It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.
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论文发表日期：2021-04-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 119-126 )
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