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Sexual dimorphism in vascular ATP‐sensitive K+ channel function supporting interstitial PO2 via convective and/or diffusive O2 transport

Inhibition of pancreatic ATP‐sensitive K+ (KATP) channels is the intended effect of oral sulphonylureas to increase insulin release in diabetes. However, pertinent to off‐target effects of sulphonylurea medication, sex differences in cardiac KATP channel function exist, whereas potential sex differences in vascular KATP channel function remain unknown. In the present study, we assessed vascular KATP channel function (topical glibenclamide superfused onto fast‐twitch oxidative skeletal muscle) supporting blood flow and interstitial O2 delivery‐utilization matching ( PO2is) during twitch contractions in male, female during pro‐oestrus and ovariectomized female (F+OVX) rats. Glibenclamide decreased blood flow (convective O2 transport) and interstitial PO2 in male and female, but not F+OVX, rats. Compared to males, females also demonstrated impaired diffusive O2 transport and a faster fall in interstitial PO2 . Our demonstration, in rats, that sex differences in vascular KATP channel function exist support the tentative hypothesis that oral sulphonylureas may exacerbate exercise intolerance and morbidity, especially in premenopausal females.