Interstitial PO2 Dynamics During Contractions in Healthy Skeletal Muscle: Relationship to Oxidative Capacity and Nitric Oxide Bioavailability
Authors: Colburn Trenton D. , Craig Jesse C. , Hirai Daniel M. , Tabuchi Ayaka , Hageman K. Sue , Musch Timothy I. , Poole David C. 
Published: June 2021

Exercise tolerance is dependent upon O2 availability for mitochondrial ATP production with compromised O2 delivery inducing a cascade of fatigue‐related processes. Within contracting muscles a principal site of limitation to blood‐myocyte O2 flux is in the O2‐carrier deficient interstitial space (is) between the capillary and sarcolemma. We utilized a novel phosphorescence probe to measure O2 pressure in this space (i.e., PO2is) in two distinctly different fast twitch muscles, the peroneal (PER, high oxidative capacity) and white gastrocnemius (WG, low oxidative capacity) at rest and following the onset of contractions. We speculated that the two muscles would exhibit contrasting PO2is profiles and that nitric oxide (NO) bioavailability would be of greater importance to the highly oxidative PER.

PURPOSE

To determine the relationship between oxidative capacity (citrate synthase: PER ~20 vs WG ~8–11 μmol/min/g) and PO2is dynamics following the onset of contractions in muscles of similar fiber‐type (86% and 100% type IId/x+IIb, PER and WG respectively). We hypothesized that the more oxidative PER muscle would have a higher resting PO2is and, during contractions, would display faster kinetics (time to reach 63% of final response (τ) and mean response time (MRT)) to an elevated nadir PO2is compared to WG. In addition, increased NO bioavailability via sodium nitroprusside (SNP; NO donor) was hypothesized to elevate PO2is in both muscles across all time points (baseline (BL), nadir, end contractions) whereas NO synthase inhibition via L‐nitroarginine methyl ester (L‐NAME) would reduce PER but not WG PO2is.

METHODS

PO2is was determined via phosphorescence quenching (Oxyphor G4) in the exposed rat PER and WG (n=8) at rest and following onset of electrically‐stimulated muscle contractions (1 Hz, 8 V, 3 min) under control (CON), SNP and L‐NAME superfusion.

RESULTS

PO2is was significantly higher in PER compared to WG at rest (PO2is (BL): 17.7 ± 2.7 vs. 9.7 ± 1.3 mmHg, p≤0.05). Following the onset of contractions, PER PO2is fell with faster dynamics (τ: 11.4 ± 0.9 vs. 17.6 ± 2.2 s; MRT: 14.8 ± 1.4 vs. 20.4 ± 2.4 s, PER vs WG respectively) to an elevated nadir (8.3 ± 1.4 vs. 3.5 ± 0.6 mmHg) and end contractions level (11.8 ± 1.0 vs. 4.6 ± 0.7 mmHg; p≤0.05 for all) compared to WG. SNP elevated PO2is across all time points (p≤0.05 for all). L‐NAME did not alter WG PO2is (p>0.05) but decreased PER nadir (CON: 8.3 ± 1.4 vs. L‐NAME: 5.7 ± 1.1 mmHg) and end contraction PO2is (CON: 11.8 ± 1.0 vs. L‐NAME: 8.9 ± 1.1 mmHg; p≤0.05 for both).

CONCLUSIONS

Consistent with our hypothesis the more oxidative PER displayed higher interstitial‐mitochondrial driving pressures (PO2is) at rest and during contractions and faster PO2is kinetics following contractions onset. We surmise that this occurred due to greater O2 flux in combination with a substantial capillary‐interstitium resistance. Furthermore, NO synthase inhibition reduced PO2is during contractions in PER, but not WG, indicating that PO2is in fast‐twitch oxidative muscle is, in part, dependent on endogenous NO bioavailability.

Support or Funding Information

NIH HL‐2‐108328

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.