Lasse Gliemann

Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men

•  In rodents, resveratrol has been shown to enhance training‐induced changes in cardiovascular function, exercise performance and the retardation of atherosclerosis. We examined the effect of 8 weeks of exercise training with and without concomitant resveratrol supplementation in aged men. •  Exercise training potently improved blood pressure, blood cholesterol, maximal oxygen uptake and the plasma lipid profile. •  Resveratrol supplementation reduced the positive effect of exercise training on blood pressure, blood cholesterol and maximal oxygen uptake and did not affect the retardation of atherosclerosis. •  Whereas exercise training improved formation of the vasodilator prostacyclin, concomitant resveratrol supplementation caused a shift in vasoactive systems favouring vasoconstriction. •  The present study is the first to demonstrate negative effects of resveratrol on training‐induced improvements in cardiovascular health parameters in humans and adds to the growing body of evidence questioning the positive effects of resveratrol supplementation in humans.

Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men

Ageing is associated with lifestyle‐related metabolic diseases, and exercise training has been suggested to counteract such metabolic deteriorations. The natural antioxidant resveratrol has been reported to exert ‘exercise‐like’ health beneficial metabolic and anti‐inflammatory effects in rodents, but little is known about the metabolic effects of resveratrol supplementation alone and in combination with exercise training in humans. The present findings showed that exercise training markedly improved muscle endurance, increased content and activity of oxidative proteins in skeletal muscle and reduced markers of oxidative stress and inflammation in skeletal muscle of aged men. Resveratrol alone did not elicit metabolic effects in healthy aged subjects, but even impaired the exercise training‐induced improvements in markers of oxidative stress and inflammation in skeletal muscle.

Exercise training modulates functional sympatholysis and α-adrenergic vasoconstrictor responsiveness in hypertensive and normotensive individuals.

Essential hypertension is linked to an increased sympathetic vasoconstrictor activity and reduced tissue perfusion. Exercise training can improve the ability to override sympathetic vasoconstrictor activity. Here we show that 8 weeks of exercise training reduces the vasoconstrictor response to sympathetic nerve activity (induced by tyramine) and improves the ability to override sympathetic vasoconstrictor activity. We found no difference in the ability to override sympathetic vasoconstrictor activity during exercise, the reduction in blood flow in response to increases in sympathetic nerve activity or the hyperaemic response to infused ATP between normo‐ and hypertensive subjects. These results help us to better understand how exercise training can reduce blood pressure and improve tissue perfusion.

Nitric oxide and reactive oxygen species in limb vascular function: what is the effect of physical activity?

Abstract Nitric oxide (NO) is known to be one of the most important regulatory compounds within the cardiovascular system where it is central for functions such as regulation of blood pressure, blood flow, and vascular growth. The bioavailability of NO is determined by a balance between, on one hand, the extent of enzymatic and non-enzymatic formation of NO and on the other hand, removal of NO, which in part is dependent on the reaction of NO with reactive oxygen species (ROS). The presence of ROS is dependent on the extent of ROS formation via mitochondria and/or enzymes such as NAD(P)H oxidase (NOX) and xanthine oxidase (XO) and the degree of ROS removal through the antioxidant defense system or other reactions. The development of cardiovascular disease has been proposed to be closely related to a reduced bioavailability of NO in parallel with an increased presence of ROS. Excessive levels of ROS not only lower the bioavailability of NO but may also cause cellular damage in the cardiovascular system. Physical activity has been shown to greatly improve cardiovascular function, in part through improved bioavailability of NO, enhanced endogenous antioxidant defense and a lowering of the expression of ROS-forming enzymes. Regular physical activity is therefore likely to be a highly useful tool in the treatment of cardiovascular disease. Future studies should focus on which form of exercise may be most optimal for enhancing NO bioavailability and improving cardiovascular health.

Effects of Exercise Training on Regulation of Skeletal Muscle Glucose Metabolism in Elderly Men

BACKGROUND The aim was to investigate the molecular mechanisms behind exercise training-induced improvements in glucose regulation in aged subjects. METHODS Twelve elderly male subjects completed 8 weeks of exercise training. Before and after the training period, the subjects completed an oral glucose tolerance test (OGTT) and a muscle biopsy was obtained from the vastus lateralis before and 45 minutes into the OGTT. Blood samples were collected before and up to 120 minutes after glucose intake. RESULTS Exercise training increased Hexokinase II, GLUT4, Akt2, glycogen synthase (GS), pyruvate dehydrogenase (PDH)-E1α, PDK2 protein, and glycogen content in skeletal muscle. Furthermore, in response to glucose, GS activity was increased and the dephosphorylation of GS site 2 + 2a and 3a was enhanced after the training intervention. The glucose-mediated insulin stimulation of TBC1D4 Thr(642) phosphorylation was increased after exercise training. In the trained state, the PDHa activity was reduced following glucose intake and without changes in phosphorylation level of PDH-E1α. CONCLUSIONS The present results suggest that exercise training improves glucose regulation in elderly subjects by enhancing the capacity and acute regulation of glucose uptake and by enhancing intracellular glucose removal to glycogen synthesis rather than glucose oxidation.

Impact of training status on LPS-induced acute inflammation in humans

The aim of the present study was to examine the impact of training status on the ability to induce a lipopolysaccharide (LPS)-induced inflammatory response systemically as well as in skeletal muscle (SkM) and adipose tissue (AT) in human subjects. Seventeen young (23.8 ± 2.5 yr of age) healthy male subjects were included in the study with eight subjects assigned to a trained (T) group and nine subjects assigned to an untrained (UT) group. On the experimental day, catheters were inserted in the femoral artery and vein of one leg for blood sampling and a bolus of 0.3 ng LPS/kg body wt was injected into an antecubital vein in the forearm. Femoral arterial blood flow was measured by ultrasound Doppler, and arterial and venous blood samples were drawn before (Pre) LPS injection and 30, 60, 90, and 120 min after the LPS injection. Vastus lateralis muscle and abdominal subcutaneous AT biopsies were obtained Pre and 60 and 120 min after the LPS injection. LPS increased the systemic plasma TNFα and IL-6 level as well as the TNFα and IL-6 mRNA content in SkM and AT of both UT and T. However, whereas the LPS-induced inflammatory response in SkM was enhanced in T subjects relative to UT, the inflammatory response systemically and in AT was somewhat delayed in T subjects relative to UT. The present findings highlight that training status affects the ability to induce a LPS-induced acute inflammatory response in a tissue-specific manner.

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

In animal studies, the polyphenol resveratrol has been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim of the present study was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Forty-three healthy physically inactive aged men (65 ± 1 yr) were divided into 1) a training group that conducted 8 wk of intense exercise training where half of the subjects received a daily intake of either 250 mg trans-resveratrol (n = 14) and the other half received placebo (n = 13) and 2) a nontraining group that received either 250 mg trans-resveratrol (n = 9) or placebo (n = 7). The group that trained with placebo showed a ~20% increase in the capillary-to-fiber ratio, an increase in muscle protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle interstitial VEGF and thrombospodin-1 protein levels were unchanged after the training period. The group that trained with resveratrol supplementation did not show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol group than in the training and placebo group. Both training groups showed an increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was lower in the resveratrol-treated group than the placebo-treated group after 8 wk. In conclusion, these data show that exercise training has a strong angiogenic effect, whereas resveratrol supplementation may limit basal and training-induced angiogenesis.

Capillary growth, ultrastructure remodelling and exercise training in skeletal muscle of essential hypertensive patients

The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters.

10-20-30 training increases performance and lowers blood pressure and VEGF in runners.

The present study examined the effect of training by the 10‐20‐30 concept on performance, blood pressure (BP), and skeletal muscle angiogenesis as well as the feasibility of completing high‐intensity interval training in local running communities. One hundred sixty recreational runners were divided into either a control group (CON; n = 28), or a 10‐20‐30 training group (10‐20‐30; n = 132) replacing two of three weekly training sessions with 10‐20‐30 training for 8 weeks and performance of a 5‐km run (5‐K) and BP was measured. VO2max was measured and resting muscle biopsies were taken in a subgroup of runners (n = 18). 10‐20‐30 improved 5‐K time (38 s) and lowered systolic BP (2 ± 1 mmHg). For hypertensive subjects in 10‐20‐30 (n = 30), systolic and diastolic BP was lowered by 5 ± 4 and 3 ± 2 mmHg, respectively, which was a greater reduction than in the non‐hypertensive subjects (n = 102). 10‐20‐30 increased VO2max but did not influence muscle fiber area, distribution or capillarization, whereas the expression of the pro‐angiogenic vascular endothelial growth factor (VEGF) was lowered by 22%. No changes were observed in CON. These results suggest that 10‐20‐30 training is an effective and easily implemented training intervention improving endurance performance, VO2max and lowering BP in recreational runners, but does not affect muscle morphology and reduces muscle VEGF.

Vascular function in health, hypertension, and diabetes: effect of physical activity on skeletal muscle microcirculation

Regulation of skeletal muscle blood flow is a complex process, which involves an integration of multiple mechanisms and a number of vasoactive compounds. Overall, muscle blood flow is regulated through a balance between vasoconstrictor and vasodilator signals. In a healthy cardiovascular system, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular function by enhancing vasodilator formation and reducing the levels of vasoconstrictors and ROS.