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To test this hypothesis, we evaluated vascular function in response to hindlimb muscle contraction, and the contribution of KCa channels in anaesthetised ZFDM, metabolic disease rats with type 2 diabetes. We also tested whether exercise training ameliorated the vascular response. Using <jats:italic>in vivo<\/jats:italic> microangiography, the hindlimb vasculature was visualized before and after rhythmic muscle contraction (0.5\u00a0s tetanus every 3\u00a0s, 20 times) evoked by sciatic nerve stimulation (40\u00a0Hz). Femoral blood flow of the contracting hindlimb was simultaneously measured by an ultrasonic flowmeter. The contribution of KCa channels was investigated in the presence and absence of apamin and charybdotoxin. We found that vascular and blood flow responses to muscle contraction were significantly impaired at the level of small artery segments in ZFDM fa\/fa rats compared to its lean control fa\/+ rats. The contribution of KCa channels was also smaller in fa\/fa than in fa\/+ rats. Low\u2010intensity exercise training for 12\u00a0weeks in fa\/fa rats demonstrated minor changes in the vascular and blood flow response to muscle contraction. However, the KCa\u2010derived component in the response to muscle contraction was much greater in exercise trained than in sedentary fa\/fa rats. These data suggest that exercise training increases the contribution of KCa channels among endothelium\u2010dependent vasodilatory mechanisms to maintain vascular and blood flow responses to muscle contraction in this metabolic disease rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Microvascular dysfunction in type 2 diabetes impairs blood flow redistribution during exercise and limits the performance of skeletal muscle and may cause early fatigability.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Endothelium\u2010dependent hyperpolarization (EDH), which mediates vasodilatation in resistance arteries, is known to be depressed in animals with diabetes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here, we report that low\u2010intensity exercise training in ZFDM rats increased the KCa channel\u2010derived component in the vasodilator responses to muscle contraction compared to that in sedentary rats, partly as a result of the increase in KCNN3 expression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that low\u2010intensity exercise training improves blood flow redistribution in contracting skeletal muscle in metabolic disease with diabetes via upregulation of EDH.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282981","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:54:37Z","timestamp":1652403277000},"page":"2919-2938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM 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