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Vascular ATP-sensitive K+ channels support maximal aerobic capacity and critical speed via convective and diffusive O2 transport.

Trenton D ColburnRamona E WeberK Sue HagemanJacob T CaldwellKiana M SchulzeCarl J AdeBrad J BehnkeDavid C PooleTimothy I Musch
Published in: The Journal of physiology (2020)
Vascular ATP-sensitive K+ (KATP ) channels support skeletal muscle blood flow and microvascular oxygen delivery-to-utilization matching during exercise. However, oral sulphonylurea treatment for diabetes inhibits pancreatic KATP channels to enhance insulin release. Herein we tested the hypotheses that: i) systemic KATP channel inhibition via glibenclamide (GLI; 10 mg kg-1 i.p.) would decrease cardiac output at rest (echocardiography), maximal aerobic capacity ( V ̇ O2 max) and the speed-duration relationship (i.e. lower critical speed (CS)) during treadmill running; and ii) local KATP channel inhibition (5 mg kg-1 GLI superfusion) would decrease blood flow (15 µm microspheres), interstitial space oxygen pressures (PO2 is; phosphorescence quenching) and convective and diffusive O2 transport ( Q ̇ O2 and DO2 , respectively; Fick Principle and Law of Diffusion) in contracting fast-twitch oxidative mixed gastrocnemius muscle (MG: 9% type I+IIa fibres). At rest, GLI slowed left ventricular relaxation (2.11 ± 0.59 vs. 1.70 ± 0.23 cm s-1 ) and decreased heart rate (321 ± 23 vs. 304 ± 22 bpm, both P < 0.05) while cardiac output remained unaltered (219 ± 64 vs. 197 ± 39 ml min-1 , P > 0.05). During exercise, GLI reduced V ̇ O2 max (71.5 ± 3.1 vs. 67.9 ± 4.8 ml kg-1 min-1 ) and CS (35.9 ± 2.4 vs. 31.9 ± 3.1 m min-1 , both P < 0.05). Local KATP channel inhibition decreased MG blood flow (52 ± 25 vs. 34 ± 13 ml min-1 100 g tissue-1 ) and PO2 isnadir (5.9 ± 0.9 vs. 4.7 ± 1.1 mmHg) during twitch contractions. Furthermore, MG V ̇ O2 was reduced via impaired Q ̇ O2 and DO2 (P < 0.05 for each). Collectively, these data support that vascular KATP channels help sustain submaximal exercise tolerance in healthy rats. For patients taking sulfonylureas, KATP channel inhibition may exacerbate exercise intolerance.
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