Search

The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant of neuronal NOS, termed nNOS[micro]. Exercise training increases nNOS[micro] protein levels in rat skeletal muscle, but data in humans are conflicting. We performed two studies to determine 1) whether resting nNOS[micro] protein expression is greater in skeletal muscle of 10 endurance-trained athletes compared with 11 sedentary individuals (study 1) and 2) whether intense short-term (10 days) exercise training increases resting nNOS[micro] protein (within whole muscle and also within types I, IIa, and IIx fibers) in eight sedentary individuals (study 2). In study 1, nNOS[micro] protein was ~60% higher (P < 0.05) in endurance-trained athletes compared with the sedentary participants. In study 2, nNOS[micro] protein expression was similar in types I, IIa, and IIx fibers before training. Ten days of intense exercise training significantly (P < 0.05) increased nNOS[micro] protein levels in types I, IIa, and IIx fibers, a finding that was validated by using whole muscle samples. Endothelial NOS and inducible NOS protein were barely detectable in the skeletal muscle samples. In conclusion, nNOS[micro] protein expression is greater in endurance-trained individuals when compared with sedentary individuals. Ten days of intense exercise is also sufficient to increase nNOS[micro] expression in untrained individuals, due to uniform increases of nNOS[micro] within types I, IIa, and IIx fibers. nitric oxide; nitric oxide synthase; immunohistochemistry

The relationship between arterial circulation compliance and moderate physical activity was established through investigating the effects of a 30-min bout of cycling exercise on the indexes of arterial compliance. Results have shown that repetitious exercise can cause vascular adaptation to compensate for the increased demand in blood circulation. Vascular dilatation of the large proximal vessels was closely related to central changes, while peripheral changes were related to vasodilatation of the exercising muscular beds.

Forearm venous occlusion plethysmography was utilized to determine the role of nontrained vascular beds in mediating the effects of aerobic exercise on sedentary male volunteers. Analysis of forearm blood flow responses to aerobic exercise in sedentary male volunteers indicated the presence of elevated basal nitric oxide release. The release of nitric oxide during prolonged endurance exercise was mediated by elevations in arterial shear stress due to increased blood flow, blood viscosity, pulse pressure and heart rate.

Athletes show a higher vascular reactivity to acetylcholine compared to sedentary subjects as long-term excercise training increases the dilator reserve due to altered lipoprotein levels. The adaptations are not confined to trained muscles alone and are associated with lower plasma cholesterol in the athletic group. There are no differences between the two groups in the forearm vascular resistance responses to angiotensin II, sodium nitroprussside, norepinephrine, or N(super G)-monomethyl-L-arginine. Results have implications in situations of impaired vasodilator capacity.

Measurements of the fluxes of sympathetic neurotransmission-related neurochemicals to plasma in young and old healthy men using kinetic methods helped study the alterations in human sympathetic nervous function due to aging. Older men had a higher level of plasma norepinephrine and normal renal norepinephrine spillover. Reduced levels of tritiated norepinephrine extraction from plasma during transit through the heart in old men indicates a reduction in neuronal norepinephrine reuptake. Normal levels of norepinephrine precursor and metabolite overflow reveal that norepinephrine release and synthesis are not enhanced.

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions: 1 ) uninterrupted sitting (SIT), 2 ) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3 ) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, P < 0.001) and SRA6 (46.2 ± 4.1/s, P < 0.001) relative to SIT (33.1 ± 4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 min, but not 60 min, significantly increased mean femoral artery FMD over 7 h, relative to SIT. Our findings suggest that more frequent and shorter breaks may be more beneficial than longer, less frequent breaks for vascular health in those with T2D. NEW & NOTEWORTHY This is the first trial to examine both the effects of interrupting prolonged sitting on vascular function in type 2 diabetes and the effects of the frequency and duration of interruptions. Brief, simple resistance activity bouts every 30 min, but not every 60 min, increased mean femoral artery flow-mediated dilation over 7 h, relative to uninterrupted sitting. With further supporting evidence, these initial findings can have important implications for cardiovascular health in type 2 diabetes.

Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain mitochondrial health and function. Disruptions in mitochondrial dynamics often lead to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins, including the E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known to regulate mitochondrial dynamics; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ) during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression in vitro and in vivo alters mitochondrial function, affects cellular metabolism, and leads to differential regulation of several metabolic genes. Thus our data demonstrate an association between mitochondrial dynamics and metabolism that defines MARCH5 as a critical link between these interconnected pathways.

The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant of neuronal NOS, termed nNOS mu. Exercise training increases nNOS mu protein levels in rat skeletal muscle, but data in humans are conflicting. We performed two studies to determine 1) whether resting nNOS mu protein expression is greater in skeletal muscle of 10 endurance-trained athletes compared with 11 sedentary individuals (study 1) and 2) whether intense short-term (10 days) exercise training increases resting nNOS mu protein (within whole muscle and also within types I, IIa, and IIx fibers) in eight sedentary individuals (study 2). In study 1, nNOS mu protein was approximately 60% higher (P < 0.05) in endurance-trained athletes compared with the sedentary participants. In study 2, nNOS mu protein expression was similar in types I, IIa, and IIx fibers before training. Ten days of intense exercise training significantly (P < 0.05) increased nNOS mu protein levels in types I, IIa, and IIx fibers, a finding that was validated by using whole muscle samples. Endothelial NOS and inducible NOS protein were barely detectable in the skeletal muscle samples. In conclusion, nNOS mu protein expression is greater in endurance-trained individuals when compared with sedentary individuals. Ten days of intense exercise is also sufficient to increase nNOS mu expression in untrained individuals, due to uniform increases of nNOS mu within types I, IIa, and IIx fibers.