Hydrogen Peroxide‐Dependent Arteriolar Dilation in Contracting Muscle of Rats Fed Normal and High Salt Diets

Objective: High dietary salt intake decreases the arteriolar dilation associated with skeletal muscle contraction. Because hydrogen peroxide (H 2 O 2 ) can be released from contracting muscle fibers, this study was designed to assess the possible contribution of H 2 O 2 to skeletal muscle functional hyperemia and its sensitivity to dietary salt. Methods: The authors investigated the effect of catalase treatment on arteriolar dilation and hyperemia in contracting spinotrapezius muscle of rats fed a normal salt (0.45%, NS) or high salt (4%, HS) diet for 4 weeks. Catalase‐sensitive 2′,7′‐dichlorofluorescein (DCF) fluorescence was measured as an index of H 2 O 2 formation, and the mechanism of arteriolar dilation to H 2 O 2 was probed in each group using pharmacological inhibitors. Results: DCF fluorescence increased with muscle contraction, but not if catalase was present. Catalase also reduced arteriolar dilation and hyperemia during contraction in both dietary groups. Exogenous H 2 O 2 dilated arterioles in both groups, with greater responses in HS rats. Guanylate cyclase inhibition did not affect arteriolar responses to H 2 O 2 in either group, but K Ca or K ATP channel inhibition equally reduced these responses, and K ATP channel inhibition equally reduced functional hyperemia in both groups. Conclusions: These results indicate that locally produced H 2 O 2 contributes to arteriolar dilation and hyperemia in contracting skeletal muscle, and that the effect of H 2 O 2 on arteriolar tone in this vascular bed is mediated largely through K + channel activation. High dietary salt intake does not reduce the contribution of H 2 O 2 to active hyperemia, or alter the mechanism through which H 2 O 2 relaxes arteriolar smooth muscle.