Aging impacts microvascular oxygen pressures during recovery from contractions in rat skeletal muscle

American Journal of Physiology-Heart and Circulatory Physiology

Ferreira

et al. 2010

Self Cite

Chronic heart failure (CHF) induces muscle fiber-type specific alterations in skeletal muscle O(2) delivery and utilization during metabolic transitions. As a result, the recovery of microvascular Po(2) (Pmv(O(2))) is prolonged in slow-twitch skeletal muscle but not fast-twitch skeletal muscle in rats with CHF. We tested the hypothesis that CHF slows Pmv(O(2)) recovery in rat skeletal muscle of a mixed fiber-type analogous to human locomotory muscles and that the degree of slowing correlates with central indexes of heart failure. Healthy control [n = 6, left ventricular end-diastolic pressure (LVEDP): 10 ± 1 mmHg], moderate CHF (n = 6, LVEDP: 18 ± 2 mmHg), and severe CHF (n = 4, LVEDP: 34 ± 2 mmHg) female Sprague-Dawley rats had their right spinotrapezius muscles (41% type I, 7% type IIa, and 52% type IIb and d/x) exposed, and Pmv(O(2)) was measured via phosphorescence quenching during 180 s of recovery from 180 s of electrically induced twitch contractions (1 Hz, 4-6 V). CHF progressively slowed the mean response time (MRT; the time to reach 63% of the overall dynamic response) of Pmv(O(2)) recovery (MRT(off); control: 60.2 ± 6.9, moderate CHF: 72.8 ± 6.6, and severe CHF: 109.8 ± 6.6 s, P < 0.05 for all). MRT(off) correlated positively with central hemodynamic (LVEDP: r = 0.76, P < 0.01) and morphological (right ventricle-to-body weight ratio: r = 0.74, P < 0.01; and lung weight-to-body weight ratio: r = 0.79, P < 0.01) indexes of heart failure. The present investigation suggests that slowed Pmv(O(2)) kinetics during recovery in CHF constitutes a mechanistic link between impaired circulatory and metabolic recovery after contractions in CHF.

Section: Discussionsupporting

confidence: 88%

Progressive chronic heart failure slows the recovery of microvascular O₂pressures after contractions in the rat spinotrapezius muscle

American Journal of Physiology-Heart and Circulatory Physiology

Ferreira

et al. 2010

Self Cite

“…The MRT analysis was constrained to the first phase of the PO2mv response since inclusion of the emergent second phase underestimates the actual rate of PO2mv fall following initiation of contractions (25).…”

Section: Methodsmentioning

confidence: 99%

“…Derangements in NO-mediated function likely represent one of the main mechanisms underlying temporal Q O 2 /V O 2 mismatch during transitions in metabolic demand in aged skeletal muscle (5,16,23,25). Impairments in the ability to regulate Q O 2 relative to V O 2 diminish muscle microvascular O 2 pressures (PO 2mv ) and thus the driving force for blood-myocyte O 2 flux as dictated by Fick's law of diffusion.…”

mentioning

confidence: 99%

Effects of neuronal nitric oxide synthase inhibition on microvascular and contractile function in skeletal muscle of aged rats

American Journal of Physiology-Heart and Circulatory Physiology

Holdsworth

et al. 2012

Self Cite

Hirai DM, Copp SW, Holdsworth CT, Ferguson SK, Musch TI, Poole DC. Effects of neuronal nitric oxide synthase inhibition on microvascular and contractile function in skeletal muscle of aged rats. Am J Physiol Heart Circ Physiol 303: H1076 -H1084, 2012. First published August 24, 2012; doi:10.1152 doi:10. /ajpheart.00477.2012 age is associated with derangements in skeletal muscle microvascular function during the transition from rest to contractions. We tested the hypothesis that, contrary to what was reported previously in young rats, selective neuronal nitric oxide (NO) synthase (nNOS) inhibition would result in attenuated or absent alterations in skeletal muscle microvascular oxygenation (PO 2mv), which reflects the matching between muscle O 2 delivery and utilization, following the onset of contractions in old rats. Spinotrapezius muscle blood flow (radiolabeled microspheres), PO 2mv (phosphorescence quenching), O2 utilization (V O2; Fick calculation), and submaximal force production were measured at rest and following the onset of contractions in anesthetized old male Fischer 344 ϫ Brown Norway rats (27 to 28 mo) pre-and postselective nNOS inhibition (2.1 mol/kg S-methyl-L-thiocitrulline; SMTC). At rest, SMTC had no effects on muscle blood flow (P Ͼ 0.05) but reduced V O2 by ϳ23% (P Ͻ 0.05), which elevated basal PO 2mv by ϳ18% (P Ͻ 0.05). During contractions, steady-state muscle blood flow, V O2, PO2mv, and force production were not altered after SMTC (P Ͼ 0.05 for all). The overall PO 2mv dynamics following onset of contractions was also unaffected by SMTC (mean response time: pre, 19.7 Ϯ 1.5; and post, 20.0 Ϯ 2.0 s; P Ͼ 0.05). These results indicate that the locus of nNOS-derived NO control in skeletal muscle depends on age and metabolic rate (i.e., rest vs. contractions). Alterations in nNOS-mediated regulation of contracting skeletal muscle microvascular function with aging may contribute to poor exercise capacity in this population.aging; blood flow; force; oxygen uptake; S-methyl-L-thiocitrulline NITRIC OXIDE (NO) is a ubiquitous signaling messenger synthesized primarily through the conversion of L-arginine to L-citrulline by the enzyme NO synthase (NOS). Within skeletal muscle, NO plays a critical role in the modulation of several physiological processes including vascular relaxation, oxidative metabolism, and excitation-contraction coupling (56). All three major NOS isoforms are expressed in mammalian skeletal muscle, namely, neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) (56). Several lines of evidence indicate that NO derived from nNOS participates significantly in the matching of muscle O 2 delivery and utilization (Q O 2 /V O 2 ) at rest and during contractions as well as submaximal force production in healthy young individuals (12; see also Refs. 13,15,19,28,33,36,39,45,52,53,60).Advancing age is associated with impairments in the O 2 transport pathway and exercise capacity (47). Derangements in NO-mediated function likely represent one of the main mechanisms underlying tem...

“…The peripheral circulation is particularly susceptible to the aging process so that alterations at the level of the skeletal muscle (5-7, 9, 18, 36, 40, 47, 48, 66) contribute significantly to the impairments in blood flow and its distribution during contractions (11,26,35,49). The resultant mismatch between muscle oxygen delivery and utilization during metabolic transients in old individuals (8,29) is considered to play a fundamental role in the decline in exercise performance with aging (54,55).…”

mentioning

confidence: 99%

Aging alters the contribution of nitric oxide to regional muscle hemodynamic control at rest and during exercise in rats

Journal of Applied Physiology

Hageman³

et al. 2011

Self Cite

Advanced age is associated with altered skeletal muscle hemodynamic control during the transition from rest to exercise. This study investigated the effects of aging on the functional role of nitric oxide (NO) in regulating total, inter-, and intramuscular hindlimb hemodynamic control at rest and during submaximal whole body exercise. We tested the hypothesis that NO synthase inhibition (N(G)-nitro-l-arginine methyl ester, l-NAME; 10 mg/kg) would result in attenuated reductions in vascular conductance (VC) primarily in oxidative muscles in old compared with young rats. Total and regional hindlimb muscle VCs were determined via radiolabeled microspheres at rest and during treadmill running (20 m/min, 5% grade) in nine young (6-8 mo) and seven old (27-29 mo) male Fisher 344 × Brown Norway rats. At rest, l-NAME increased mean arterial pressure (MAP) significantly by ∼17% and 21% in young and old rats, respectively. During exercise, l-NAME increased MAP significantly by ∼13% and 19% in young and old rats, respectively. Compared with young rats, l-NAME administration in old rats evoked attenuated reductions in 1) total hindlimb VC during exercise (i.e., down by ∼23% in old vs. 43% in young rats; P < 0.05), and 2) VC in predominantly oxidative muscles both at rest and during exercise (P < 0.05). Our results indicate that the dependency of highly oxidative muscles on NO-mediated vasodilation is markedly diminished, and therefore mechanisms other than NO-mediated vasodilation control the bulk of the increase in skeletal muscle VC during the transition from rest to exercise in old rats. Reduced NO contribution to vasomotor control with advanced age is associated with blood flow redistribution from highly oxidative to glycolytic muscles during exercise.