Exercise Enhances Anti-contractile Effects of PVAT Through Endogenous H₂S in High-Fat Diet–Induced Obesity Hypertension

Hydrogen sulfide (H₂S) 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 H₂S 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 H₂S in PVAT even after exercise (HE vs. HEB, P < 0.05). Furthermore, long-term exercise altered the expressions of voltage-dependent K⁺ (K_v) 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 H₂S 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 H₂S.