Introduction The study evaluated the role of lifelong physical activity for leg vascular function in postmenopausal women (61 ± 1 yr). Method The study design was cross-sectional with three different groups based on self-reported physical activity level with regard to intensity and volume over the past decade: inactive (n = 14), moderately active (n = 12), and very active (n = 15). Endothelial-dependent and smooth muscle-dependent leg vascular function were assessed by ultrasound Doppler measurements of the femoral artery during infusion of acetylcholine (Ach), the nitric oxide (NO) donor sodium nitroprusside and the prostacyclin analog epoprostenol. Thigh muscle biopsies, arterial and venous plasma samples were obtained for assessment of vasodilator systems. Results The very active group was found to have 76% greater responsiveness to Ach compared with the sedentary group accompanied by 200% higher prostacyclin synthesis during Ach infusion. Smooth muscle cell responsiveness to sodium nitroprusside and epoprostenol was not different between groups. The protein amount of endothelial NO synthase and endogenous antioxidant enzymes in muscle tissue was higher in the very active than the inactive group. The moderately active group had a similar endothelial and smooth muscle cell responsiveness as the inactive group. A secondary comparison with a smaller group (n = 5) of habitually active young (24 ± 2 yr) women indicated that smooth muscle cell responsiveness and endothelial responsiveness are affected by age per se. Conclusions This study shows that leg vascular function and the potential to form prostacyclin and NO in late postmenopausal women, is influenced by the extent of lifelong physical activity.

The current guidelines following an acute coronary syndrome recommend dual‐antiplatelet therapy (DAPT) (aspirin plus a P2Y12 antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown whether regular exercise affects the pharmacology of DAPT. Aim To explore how exercise‐induced improvements in vascular and platelet function affect the efficacy of DAPT, in a cross‐sectional study of men with different physical activity levels (training status). Methods A total of 42 healthy, normal‐weight, middle‐aged men were divided into 3 groups: untrained, moderately trained and well‐trained. Their platelet reactivity (agonist‐induced % aggregation) was investigated in platelet‐rich plasma at rest and after inhibition with aspirin and ticagrelor and/or prostacyclin and nitric oxide added to the blood in vitro, and after physiological tests of vascular function; passive movement of the leg, flow‐mediated dilation and one‐leg knee‐extensor exercise. Vascular function of the femoral artery (changes in arterial blood flow) was assessed by ultrasound Doppler. Results Platelets from the well‐trained subjects had lower basal reactivity, a higher sensitivity to the anti‐aggregatory effects of prostacyclin and were more potently inhibited by DAPT compared to the untrained subjects. The moderately trained and well‐trained subjects had a superior vascular function compared to untrained subjects, and their platelets were more inhibited by the passive movement, flow‐mediated dilation and one‐leg knee‐extensor exercise. Discussion A habitually active lifestyle leads to an increased platelet sensitivity to pharmacological and physiological platelet inhibitors. We suggest that physical activity habits (training status) should be considered when personalizing and optimizing antithrombotic treatment strategies.

Purpose: This study aimed to evaluate the influence of lifelong regular physical activity on skeletal muscle capillarization in women. Methods: Postmenopausal women, 61±4 yr old, were divided according to self-reported physical activity level over the past 20 yrs: sedentary (SED; n = 14), moderately active (MOD; n = 12), and very active (VERY; n = 15). Leg blood flow (LBF) was determined by ultrasound Doppler, and blood samples were drawn from the femoral artery and vein for calculation of leg oxygen uptake (LVO 2 ) at rest and during one-legged knee extensor exercise. A skeletal muscle biopsy was obtained from the vastus lateralis and analyzed for capillarization and vascular endothelial growth factor (VEGF) and mitochondrial OXPHOS proteins. Platelets were isolated from venous blood and analyzed for VEGF content and effect on endothelial cell proliferation. Results: The exercise-induced rise in LBF and LVO 2 was faster (P = 0.008) in VERY compared with SED and MOD. Steady-state LBF and LVO 2 were lower (P < 0.04) in MOD and VERY compared with SED. Capillary-fiber ratio and capillary density were greater (P < 0.03) in VERY (1.65 ± 0.48 and 409.3 ± 57.5) compared with MOD (1.30 ± 0.19 and 365.0 ± 40.2) and SED (1.30 ± 0.30 and 356.2 ± 66.3). Skeletal muscle VEGF and OXPHOS complexes I, II, and V were ~1.6-fold and ~1.25-fold (P < 0.01) higher, respectively, in VERY compared with SED. Platelets from all groups induced an approximately nine-fold (P < 0.001) increase in endothelial cell proliferation. Conclusion: A very active lifestyle is associated with superior skeletal muscle exercise hemodynamics and greater potential for oxygen extraction concurrent with a higher skeletal muscle capillarization and mitochondrial capacity.

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BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand‐grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced ( P <0.05) the remote vasodilator response to intra‐arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6‐fold increase ( P <0.05) in femoral venous plasma prostacyclin levels and with a transient increase ( P <0.05) in arterial plasma levels of brain‐derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand‐grip exercise did not influence remote microvascular function. CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral‐mediated potentiation of prostacyclin formation.