Wang Chaoge, Shu Linjie, Cheng Ran, Yan Mengsi, Liang Wenhao, Zhou Jie, Shi Niujin, Chen Lidan, Peng Linyu, Huang Junhao, Hu Min, Liao Jingwen
Guangdong Provincial Key Laboratory of Sports and Health Promotion, Guangzhou Sport University, Tianhe District, 1268 Guangzhou Avenue Middle, Guangzhou, 510500, No, China.
Scientific Research Center, Guangzhou Sport University, Guangzhou, China.
Cardiovasc Drugs Ther. 2024 Aug 12. doi: 10.1007/s10557-024-07612-x.
Hydrogen sulfide (HS) secreted by perivascular adipose tissue (PVAT) is a critical vasodilator, which might be involved during the pathogenesis of hypertension. The present study aimed to investigate the exact role of HS on the regulation of PVAT anti-contraction by long-term exercise in obesity hypertension.
After the establishment of obesity hypertension (24 weeks) through a high-fat diet, male Sprague-Dawley rats were randomly assigned to control group (HC), exercise group (HE), cystathionine γ-lyase (CSE) blocking group (HCB), and exercise combined with CSE blocking group (HEB). Exercise and CSE inhibitor regimens were performed throughout 13 weeks.
After 13 weeks of intervention, blood pressure was significantly decreased by long-term exercise (HC vs. HE, P < 0.05) but not by exercise combined with the CSE inhibitor regimen. Meanwhile, the CSE inhibitor significantly blocked the production of HS in PVAT even after exercise (HE vs. HEB, P < 0.05). Furthermore, long-term exercise altered the expressions of voltage-dependent K (K) channel subunits 7 (KCNQs), which were diminished by CSE inhibition in mesenteric arteries. As for vascular tension assessment, after incubation with or without KCNQ opener (retigabine), the anti-contractile effect of PVAT (with or without transferred bath solution of PVAT) was significantly enhanced by long-term exercise and eliminated by the CSE inhibitor regimen (P < 0.05); KCNQ inhibitor (XE991) blunted this effect except for HE.
These results collectively suggest that endogenous HS is a strong regulator of the anti-contractile effect of PVAT in obesity hypertension by long-term exercise, and KCNQ in the resistance artery might be involved during this process but not the only target channel mediated by HS.
血管周围脂肪组织（PVAT）分泌的硫化氢（HS）是一种关键的血管舒张剂，可能参与高血压的发病机制。本研究旨在探讨HS在肥胖高血压患者长期运动调节PVAT抗收缩中的具体作用。
通过高脂饮食建立肥胖高血压模型（24周）后，将雄性Sprague-Dawley大鼠随机分为对照组（HC）、运动组（HE）、胱硫醚γ-裂解酶（CSE）阻断组（HCB）和运动联合CSE阻断组（HEB）。运动和CSE抑制剂方案持续进行13周。
干预13周后，长期运动可显著降低血压（HC与HE比较，P<0.05），但运动联合CSE抑制剂方案则无此效果。同时，即使在运动后，CSE抑制剂也显著阻断了PVAT中HS的产生（HE与HEB比较，P<0.05）。此外，长期运动改变了电压依赖性钾（K）通道亚基7（KCNQs）的表达，在肠系膜动脉中，CSE抑制使其表达减少。至于血管张力评估，在使用或不使用KCNQ开放剂（瑞替加滨）孵育后，长期运动显著增强了PVAT的抗收缩作用（无论是否转移PVAT浴液），而CSE抑制剂方案则消除了这种作用（P<0.05）；KCNQ抑制剂（XE991）除HE组外均减弱了这种作用。
这些结果共同表明，内源性HS是肥胖高血压患者长期运动调节PVAT抗收缩作用的重要调节因子，阻力动脉中的KCNQ可能参与此过程，但不是HS介导的唯一靶通道。
