The Role of the Activation of the TRPV1 Receptor and of Nitric Oxide in Changes in Endothelial and Cardiac Function and Biomarker Levels in Hypertensive Rats
The Role of the Activation of the TRPV1 Receptor and of Nitric Oxide in Changes in Endothelial and Cardiac Function and Biomarker Levels in Hypertensive Rats
复制标题
DOI：
10.3390/ijerph16193576
复制
发表时间：
2019-10-01
影响因子：
--
通讯作者：
del Valle-Mondragon, Leonardo
中科院分区：
文献类型：
--
作者：
Carlos Torres-Narvaez, Juan;Perez-Torres, Israel;del Valle-Mondragon, Leonardo
本研究旨在分析瞬时受体潜在1型香草素(TRPV1)激动剂辣椒素(CS)及其拮抗剂辣椒碱(CZ)对L-N-G-硝基精氨酸甲酯(L-NAME)诱导的高血压大鼠心功能、血管内皮细胞标志物和一氧化氮(NO)释放的影响。一氧化氮参与了系统性动脉高血压的病理生理学过程。检测正常血压(118+/-3 mm Hg)和高血压(165+/4 mm Hg)大鼠血清和心肌组织中一氧化氮(NO)、四氢生物蝶呤(BH4)、丙二醛(MDA)、总抗氧化能力(TAC)、环鸟苷一磷酸(CGMP)、磷酸二酯酶-3(PDE-3)的水平，以及内皮型一氧化氮合酶(ENOS)、三磷酸鸟苷环水解酶-1(GTPCH-1)、蛋白激酶B(AKT)和TRPV1的表达。在Langendorff离体心模型中，计算心脏机械性能(CMP)并定量测定冠脉流出液中NO的含量。辣椒素可升高高血压大鼠血中NO、BH4、cGMP和TAC水平，降低PDE-3和MDA水平。ENOS、GTPCH-1、TRPV1表达增加，AKT表达减少。卡萨西平减弱了这些影响。在高血压性心脏病患者中，CS治疗改善了心肌细胞化学计分。结论：H大鼠TRPV1的激活可能是改善心功能和体内NO生物利用度相关生物标志物水平的一种替代机制。
The purpose of the present study was to analyze the actions of transient receptor potential vanilloid type 1 (TRPV1) agonist capsaicin (CS) and of its antagonist capsazepine (CZ), on cardiac function as well as endothelial biomarkers and some parameters related with nitric oxide (NO) release in L-N-G-nitroarginine methyl ester (L-NAME)-induced hypertensive rats. NO has been implicated in the pathophysiology of systemic arterial hypertension (SAHT). We analyzed the levels of nitric oxide (NO), tetrahydrobiopterin (BH4), malondialdehyde (MDA), total antioxidant capacity (TAC), cyclic guanosin monophosphate (cGMP), phosphodiesterase-3 (PDE-3), and the expression of endothelial nitric oxide synthase (eNOS), guanosine triphosphate cyclohydrolase 1 (GTPCH-1), protein kinase B (AKT), and TRPV1 in serum and cardiac tissue of normotensive (118 +/- 3 mmHg) and hypertensive (H) rats (165 +/- 4 mmHg). Cardiac mechanical performance (CMP) was calculated and NO was quantified in the coronary effluent in the Langendorff isolated heart model. In hypertensive rats capsaicin increased the levels of NO, BH4, cGMP, and TAC, and reduced PDE-3 and MDA. Expressions of eNOS, GTPCH-1, and TRPV1 were increased, while AKT was decreased. Capsazepine diminished these effects. In the hypertensive heart, CMP improved with the CS treatment. In conclusion, the activation of TRPV1 in H rats may be an alternative mechanism for the improvement of cardiac function and systemic levels of biomarkers related to the bioavailability of NO.