Combined Effects of Diazoxide and Moderate-Intensity Exercise on the Restoration of Redox Balance Post-Fatigue in Fast- and Slow-Twitch Skeletal Muscles of Hypertensive Rats

Abstract

Muscle fatigue is linked to redox imbalance and worsens under hypertension due to oxidative stress. This study tested whether diazoxide and moderate exercise could protect skeletal muscles in hypertensive rats after a fatigue protocol. Hypertension increased oxidants and reduced antioxidant defenses. Both interventions, when used alone or in combination, improved antioxidant activity and reduced oxidant levels. The combined treatment showed the most potent effect, with muscle-specific differences: fast-twitch fibers responded better to exercise, while slow-twitch fibers benefited more from the combined approach. These findings demonstrate how this strategy could inform new treatments for hypertension-induced muscle dysfunction.

Muscle fatigue, defined as a decline in force generation, is closely linked to redox imbalance—a condition exacerbated by oxidative stress in hypertension. This study investigated the effects of diazoxide administration and moderate-intensity exercise on skeletal muscle redox status following a fatigue protocol in rats with hypertension. Animals were assigned to eight groups: control (CTRL), diazoxide (DZX), exercise (EX), exercise + diazoxide (EX+DZX), hypertension (HTN), hypertension + diazoxide (HTN+DZX), hypertension + exercise (HTN+EX), and hypertension + exercise + diazoxide (HTN+ EX+DZX). Hypertension was induced by a high-salt diet. Diazoxide was administered daily for 14 days, and exercise consisted of moderate treadmill running for 8 weeks. Muscle fatigue was evoked in the extensor digitorum longus (EDL) and soleus by repetitive electrical stimulation. Post-fatigue analyses included oxidant levels, catalase activity, and glutathione status. Hypertension increased oxidants and reduced antioxidant defenses in both muscle types. Exercise and diazoxide, alone or in combination, improved redox balance, with the combined treatment providing the most robust protection and exhibiting fiber-specific adaptations. These findings suggest that diazoxide combined with moderate exercise represents a promising therapeutic approach to counteract oxidative stress-related skeletal muscle dysfunction in hypertension.