内源性硫化氢通过激活瞬时受体电位阳离子通道亚家族V成员1（TRPV1）通道增强颈动脉窦压力感受器敏感性。
Endogenous Hydrogen Sulfide Enhances Carotid Sinus Baroreceptor Sensitivity by Activating the Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Channel.
作者信息
Yu Wen, Liao Ying, Huang Yaqian, Chen Selena Y, Sun Yan, Sun Chufan, Wu Yuming, Tang Chaoshu, Du Junbao, Jin Hongfang
机构信息
Department of Pediatrics, Peking University First Hospital, Beijing, China.
University of California, San Diego, La Jolla, CA.
出版信息
J Am Heart Assoc. 2017 May 16;6(5):e004971. doi: 10.1161/JAHA.116.004971.
BACKGROUND
We aimed to investigate the regulatory effects of hydrogen sulfide (HS) on carotid sinus baroreceptor sensitivity and its mechanisms.
METHODS AND RESULTS
Male Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) were used in the experiment and were given an HS donor or a cystathionine-β-synthase inhibitor, hydroxylamine, for 8 weeks. Systolic blood pressure and the cystathionine-β-synthase/HS pathway in carotid sinus were detected. Carotid sinus baroreceptor sensitivity and the functional curve of the carotid baroreceptor were analyzed using the isolated carotid sinus perfusion technique. Effects of HS on transient receptor potential cation channel subfamily V member 1 (TRPV1) expression and S-sulfhydration were detected. In SHRs, systolic blood pressure was markedly increased, but the cystathionine-β-synthase/HS pathway in the carotid sinus was downregulated in comparison to that of Wistar-Kyoto rats. Carotid sinus baroreceptor sensitivity in SHRs was reduced, demonstrated by the right and upward shift of the functional curve of the carotid baroreceptor. Meanwhile, the downregulation of TRPV1 protein was demonstrated in the carotid sinus; however, HS reduced systolic blood pressure but enhanced carotid sinus baroreceptor sensitivity in SHRs, along with TRPV1 upregulation in the carotid sinus. In contrast, hydroxylamine significantly increased the systolic blood pressure of Wistar-Kyoto rats, along with decreased carotid sinus baroreceptor sensitivity and reduced TRPV1 protein expression in the carotid sinus. Furthermore, HS-induced enhancement of carotid sinus baroreceptor sensitivity of SHRs could be amplified by capsaicin but reduced by capsazepine. Moreover, HS facilitated S-sulfhydration of TRPV1 protein in the carotid sinus of SHRs and Wistar-Kyoto rats.
CONCLUSIONS
HS regulated blood pressure via an increase in TRPV1 protein expression and its activity to enhance carotid sinus baroreceptor sensitivity.
背景
我们旨在研究硫化氢（HS）对颈动脉窦压力感受器敏感性的调节作用及其机制。
方法与结果
实验采用雄性Wistar-Kyoto大鼠和自发性高血压大鼠（SHR），给予HS供体或胱硫醚-β-合酶抑制剂羟胺8周。检测收缩压和颈动脉窦中的胱硫醚-β-合酶/HS途径。采用离体颈动脉窦灌注技术分析颈动脉窦压力感受器敏感性和颈动脉压力感受器的功能曲线。检测HS对瞬时受体电位阳离子通道亚家族V成员1（TRPV1）表达和S-硫氢化的影响。与Wistar-Kyoto大鼠相比，SHR的收缩压显著升高，但颈动脉窦中的胱硫醚-β-合酶/HS途径下调。SHR的颈动脉窦压力感受器敏感性降低，表现为颈动脉压力感受器功能曲线右移和上移。同时，颈动脉窦中TRPV1蛋白表达下调；然而，HS降低了SHR的收缩压，但增强了颈动脉窦压力感受器敏感性，同时颈动脉窦中TRPV1上调。相反，羟胺显著升高了Wistar-Kyoto大鼠的收缩压，同时降低了颈动脉窦压力感受器敏感性，并降低了颈动脉窦中TRPV1蛋白表达。此外，辣椒素可增强HS诱导的SHR颈动脉窦压力感受器敏感性，而辣椒素拮抗剂可降低其敏感性。此外，HS促进了SHR和Wistar-Kyoto大鼠颈动脉窦中TRPV1蛋白的S-硫氢化。
结论
HS通过增加TRPV1蛋白表达及其活性来调节血压，从而增强颈动脉窦压力感受器敏感性。
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