Effects of altered nitric oxide availability on rat muscle microvascular oxygenation during contractions

Ferreira, Leonardo F.; Padilla, Danielle J.; Williams, J. B.; Hageman, K. Sue; Musch, Timothy I.; Poole, David C.

doi:10.1111/j.1748-1716.2006.01523.x

Cited by 38 publications

(44 citation statements)

References 71 publications

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“…18, 64), SMTC was always the last condition to prevent residual effects on vascular and skeletal muscle function. Importantly, there is no ordering (priming) effect on the PO2mv response to muscle contractions when a minimum of 20 min of recovery is allowed between stimulations (7,16).…”

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.…”

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confidence: 99%

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

Hirai

Copp

Holdsworth

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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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...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Hirai

Copp

Holdsworth

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

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“…Within the peripheral vasculature, NO constitutes a critical modulator of active skeletal muscle blood flow distribution (22) and the skeletal muscle O 2 delivery-to-O 2 utilization [O 2 uptake (V O 2 )] ratio, which sets the microvascular partial pressure of O 2 (PO 2mv ), and represents the pressure head for capillary-myocyte O 2 flux (11). Reduced NO bioavailability (as found in many chronic disease conditions such as diabetes, chronic heart failure, peripheral artery disease, etc.)…”

mentioning

confidence: 99%

(−)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats

Copp

White

Hirai

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓~5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min(-1)·100 g(-1), P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min(-1)·100 g(-1)·mmHg(-1), P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓~16%) but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg(-1)·day(-1)) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.

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“…Assuming that a larger area under the D[deoxy-Hb ? Mb] OS would be conceptually similar to a greater ''undershoot'' in microvascular PO 2 (Kindig et al 1999;Ferreira et al 2006) and, as we recently demonstrate on a modelling study (Barbosa et al 2010), quantitatively related to impaired capillary blood flow (Ferreira et al 2005a), this variable was used as an index of impaired microvascular O 2 delivery. The AOS was calculated in arbitrary units (a.u.)…”

Section: Discussionmentioning

confidence: 99%

“…Mb]) by nearinfrared spectroscopy) (Grassi et al 2003;DeLorey et al 2005;Ferreira et al 2005a, b;duManoir et al 2010). Central to this reasoning is the assumption that D[deoxyHb/Mb] represents a mirror image of microvascular O 2 pressure (PO 2 mv) (Kindig et al 1999;Ferreira et al 2006). Therefore, faster and heightened ([deoxy-Hb ?…”

Section: Introductionmentioning

confidence: 98%

Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

et al. 2011

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Impaired O(2) delivery relative to O(2) demands at the onset of exercise might influence the response profile of muscle fractional O(2) extraction (≅Δ[deoxy-Hb/Mb] by near-infrared spectroscopy) either by accelerating its rate of increase or creating an "overshoot" (OS) in patients with pulmonary arterial hypertension (PAH). We therefore assessed the kinetics of O(2) uptake [Formula: see text] Δ[deoxy-Hb/Mb] in the vastus lateralis, and heart rate (HR) at the onset of heavy-intensity exercise in 14 females with PAH (connective tissue disease, IPAH, portal hypertension, and acquired immunodeficiency syndrome) and 11 age- and gender-matched controls. Patients had slower [Formula: see text] and HR dynamics than controls (τ[Formula: see text] = 62.7 ± 15.2 s vs. 41.0 ± 13.8 s and t (1/2)-HR = 61.3 ± 16.6 s vs. 43.4 ± 8.8 s, respectively; p < 0.01). No study participant had a significant reduction in oxyhemoglobin saturation. In OS(-) subjects (6 patients and 7 controls), the kinetics of Δ[deoxy-Hb/Mb] relative to [Formula: see text] were faster in patients (p = 0.05). Larger area under the OS and slower kinetics (MRT) of the "downward" component indicated greater O(2) delivery-to-utilization mismatch in OS(+) patients versus OS(+) controls (477.4 ± 330.0 vs. 78.1 ± 65.6 a.u. and 74.6 ± 18.8 vs. 46.0 ± 17.0 s, respectively; p < 0.05). Resting pulmonary vascular resistance was higher in OS(+) than OS(-) patients (23.1 ± 12.0 vs. 10.7 ± 4.0 Woods, respectively; p < 0.05). We conclude that microvascular O(2) delivery-to-utilization inequalities slowed the rate of adaptation of aerobic metabolism at the start of heavy-intensity exercise in women with PAH.

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Effects of altered nitric oxide availability on rat muscle microvascular oxygenation during contractions

Abstract: These results indicate that NO availability can significantly affect P(O2)mv at rest and during contractions and suggests that P(O2)mv derangements in ageing and chronic disease conditions may potentially result from impairments in NO availability.

Cited by 38 publications

References 71 publications

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

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

(−)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats

Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

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