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Key points• 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.Abstract Ageing is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which in animal studies has been shown to decrease atherosclerosis, and improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; body mass index: 25.4 ± 0.7 kg m −2 ; mean arterial pressure (MAP): 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O 2 min −1 ) were randomized into 8 weeks of either daily intake of either 250 mg trans-resveratrol (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise training. Exercise training led to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (−4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 vs. 1174 ± 121 pg ml −1 ; P < 0.02) and muscle thromboxane synthase was higher in the resveratrol group after training (P < 0.05). Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein, total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood (P < 0.05). Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 (VCAM-1). Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation can blunt these effects.

Reductions in systemic and locomotor limb muscle blood flow and O 2 delivery limit aerobic capacity in humans. To examine whether O 2 delivery limits both aerobic power and capacity, we first measured systemic haemodynamics, O 2 transport and O 2 uptake (V O 2 ) during incremental and constant (372 ± 11 W; 85% of peak power; mean ± S.E.M.) cycling exercise to exhaustion (n = 8) and then measured systemic and leg haemodynamics andV O 2 during incremental cycling and knee-extensor exercise in male subjects (n = 10). During incremental cycling, cardiac output (Q) and systemic O 2 delivery increased linearly to 80% of peak power (r 2 = 0.998, P < 0.001) and then plateaued in parallel to a decline in stroke volume (SV) and an increase in central venous and mean arterial pressures (P < 0.05). In contrast, heart rate andV O 2 increased linearly until exhaustion (r 2 = 0.993; P < 0.001) accompanying a rise in systemic O 2 extraction to 84 ± 2%. In the exercising legs, blood flow and O 2 delivery levelled off at 73-88% of peak power, blunting legV O 2 per unit of work despite increasing O 2 extraction. When blood flow increased linearly during one-legged knee-extensor exercise,V O 2 per unit of work was unaltered on fatigue. During constant cycling,Q, SV, systemic O 2 delivery andV O 2 reached maximal values within ∼5 min, but dropped before exhaustion (P < 0.05) despite increasing or stable central venous and mean arterial pressures. In both types of maximal cycling, the impaired systemic O 2 delivery was due to the decline or plateau inQ because arterial O 2 content continued to increase. These results indicate that an inability of the circulatory system to sustain a linear increase in O 2 delivery to the locomotor muscles restrains aerobic power. The similar impairment in SV and O 2 delivery during incremental and constant load cycling provides evidence for a central limitation to aerobic power and capacity in humans.

Prostaglandins, nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs) are substances that have been proposed to be involved in the regulation of skeletal muscle blood flow during physical activity. We measured haemodynamics, plasma ATP andV O 2 at rest and during one-legged knee-extensor exercise (19 ± 1 W) in nine healthy subjects with and without intra-arterial infusion of indomethacin (Indo; 621 ± 17 μg min