Changes in the PO₂‐dependence of oxygen consumption in the skeletal muscle of developing rats

Abstract

A continuous supply of O2 to cells in a mammalian organism is necessary to maintain normal physiological function and the microcirculation is especially important in this matter as it is the site of O2 exchange. Under conditions of active/functional hyperemia following muscle contraction, the O2 transport system in older subjects does not appear to respond as rapidly and to the same degree as in younger subjects. With aging, elements of the O2 transport and regulatory system are changed in such a way that matching O2 supply to O2 demand does not work as well in older as in younger subjects. With regard to the O2 demand component of the overall system, in vitro studies have shown that oxygen consumption (VO2) remains constant until a critical partial pressure (Pcrit) of O2 (<1 mmHg) is reached. This knowledge was predicated on the assumption that the in vitro studies mimicked conditions in living tissue. More recently, however, in vivo studies have shown that VO2 varies over a much wider range of O2 partial pressure in the interstitial fluid (PISFO2). An intravital microscopic approach is being used to show that developmental changes in the O2 transport system begin earlier than previously thought. Significant and rapid changes in the microvascular network of skeletal muscle have been observed during the first few weeks of postnatal development. Three different developmental groups of male Sprague‐Dawley rats (2, 4, and 6 months) were used to investigate early changes in the O2 demand component of the transport system by measuring VO2 and the PISFO2 dependence of VO2 under resting conditions. VO2 of the spinotrapezius muscle was measured with a quasi‐continuous, flash‐synchronized, rapidly pressurized airbag system to briefly arrest blood flow and determine the rate of decrease of oxygen tension (dPO2/dt) in the ISF bathing the skeletal muscle fibers. Changes in PISFO2 of the skeletal muscle were measured using phosphorescence quenching microscopy. To understand the PO2 dependence of VO2, VO2 data were plotted versus PO2 and the results analyzed using a generalization of Michaelis‐Menten kinetics. This yielded information about both maximum VO2 (Vmax) and the PO2 at half Vmax (P50). Experiments were carried out on 16 animals with average weights (mean ± SEM) from 280 ± 10, 408 ± 17, to 454 ± 6 grams at 2 mo, 4 mo, and 6 mo, respectively. Average Vmax (mean ± SEM) was 138 ± 9, 148 ± 15, to 122 ± 6 nL O2/cm3·s for 2 mo, 4 mo, and 6 mo, respectively. Between 2 mo and 6 mo, there was a downward trend with Vmax which was not significant. Average P50 (mean ± SEM) was 11 ± 1, 15 ± 1, to 21 ± 1 mmHg for 2 mo, 4 mo, and 6 mo, respectively. There was a significant (p < 0.05) increase in P50 from 2 mo to 6 mo which indicates that as the developmental age of the animal increases, there is an increased sensitivity of O2 consumption to changes in PISFO2. The findings are consistent with published data indicating that VO2 depends on PISFO2 over a much wider physiological range than previously thought. It is clear that as the rat develops, it consumes less O2 which may be ascribed to some combination of changes in the O2 delivery system and mitochondrial function.Support or Funding InformationSupport from Department of Physiology and BiophysicsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.