Sexual dimorphism in vascular ATP-sensitive K+ channel function supporting interstitial P O 2 via convective and/or diffusive O2 transport.

Vascular ATP-sensitive K+ (KATP ) channels support skeletal muscle blood flow ( Q ̇ m ), interstitial O2 delivery ( Q ̇ O 2 )-utilization ( V ̇ O 2 ) matching (i.e. interstitial-myocyte O2 flux driving pressure; P O 2 is) and exercise tolerance. Potential sex differences in skeletal muscle vascular KATP channel function remain largely unexplored. We hypothesized that local skeletal muscle KATP channel inhibition via glibenclamide superfusion (5 mg kg-1 GLI; sulphonylurea diabetes medication) in anaesthetized female Sprague-Dawley rats, compared to males, would demonstrate greater reductions in contracting (1 Hz, 7 V, 180 s) fast-twitch oxidative mixed gastrocnemius (97% type IIA+IID/X+IIB) Q ̇ m (15 μm microspheres) and P O 2 is (phosphorescence quenching), resulting from more compromised convective ( Q ̇ O 2 ) and diffusive ( D O 2   ) O2 conductances. Furthermore, these GLI-induced reductions in ovary-intact females measured during pro-oestrus would be diminished following ovariectomy (F+OVX). GLI similarly impaired mixed gastrocnemius V ̇ O 2 in both males (↓28%) and females (↓33%, both P < 0.032) via reduced Q ̇ m (male: ↓31%, female: ↓35%, both P < 0.020), Q ̇ O 2 (male: 5.6 ± 0.5 vs. 4.0 ± 0.5, female: 6.4 ± 1.1 vs. 4.2 ± 0.6 mL O2  min-1 100 g tissue-1 , P < 0.022) and the resulting P O 2 is, with females also demonstrating a reduced D O 2   (0.40 ± 0.07 vs. 0.30 ± 0.04 mL O2  min-1 100 g tissue-1 , P < 0.042) and a greater GLI-induced speeding of P O 2 is fall (mean response time: Sex × Drug interaction, P = 0.026). Conversely, GLI did not impair the mixed gastrocnemius of F+OVX rats. Therefore, in patients taking sulphonylureas, these results support the potential for impaired vascular KATP channel function to compromise muscle Q ̇ m and therefore exercise tolerance. Such an effect, if present, would likely contribute to adverse cardiovascular events in premenopausal females more than males.