Acute antioxidant supplementation and skeletal muscle vascular conductance in aged rats: role of exercise and fiber type

Abstract

Age-related increases in oxidative stress contribute to impaired skeletal muscle vascular control. However, recent evidence indicates that antioxidant treatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) attenuates flow-mediated vasodilation in isolated arterioles from the highly oxidative soleus muscle of aged rats. Whether antioxidant treatment with tempol evokes similar responses in vivo at rest and during exercise in senescent individuals and whether this effect varies based on muscle fiber type composition are unknown. We tested the hypothesis that redox modulation via acute systemic tempol administration decreases vascular conductance (VC) primarily in oxidative hindlimb locomotor muscles at rest and during submaximal whole body exercise (treadmill running at 20 m/min, 5% grade) in aged rats. Eighteen old (25-26 mo) male Fischer 344 x Brown Norway rats were assigned to either rest (n = 8) or exercise (n = 10) groups. Regional VC was determined via radiolabeled microspheres before and after intra-arterial administration of tempol (302 μmol/kg). Tempol decreased mean arterial pressure significantly by 9% at rest and 16% during exercise. At rest, similar VC in 26 out of 28 individual hindlimb muscles or muscle parts following tempol administration compared with control resulted in unchanged total hindlimb muscle VC (control: 0.18 ± 0.02; tempol: 0.17 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1); P > 0.05). During exercise, all individual hindlimb muscles or muscle parts irrespective of fiber type composition exhibited either an increase or no change in VC with tempol (i.e., ↑11 and ↔17 muscles or muscle parts), such that total hindlimb VC increased by 25% (control: 0.93 ± 0.04; tempol: 1.15 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1); P ≤ 0.05). These results demonstrate that acute systemic administration of the antioxidant tempol significantly impacts the control of regional vascular tone in vivo presumably via redox modulation and improves skeletal muscle vasodilation independently of fiber type composition during submaximal whole body exercise in aged rats.

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

“…This shift in the muscle NOS isoform profile with aging is hallmarked by oxidative stress and endothelial dysfunction (14,24,26,54,59,61,65), which likely contribute to exercise intolerance in this population (47).…”

Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-A mice

“…Type I and type IIa fibers have high insulin sensitivity and express high levels of GLUT4, whereas type IIb fibers have low insulin sensitivity and GLUT4 expression (Henriksen et al 1990;James et al 1989). In previous reports, the soleus muscle was composed mainly of type I fibers, and the EDL muscle was composed of type IIa and IIb fibers (Burkholder et al 1994;Hirai et al 2011). Thus, the soleus muscle is rich in oxidative fiber, and the EDL muscle is high in glycolytic fiber.…”

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

“…Consequently, pharmacological (e.g., antioxidants, tetrahydrobiopterin; Refs. 21,22,27,30,58,65,67) and/or nonpharmacological (e.g., exercise training; Refs. 13, 17, 46, 58 -60, 64) interventions aiming at improving endothelial function and/or NO bioavailability could mitigate age-related blood flow redistribution and increase exercise capacity.…”