Acute impact of aerobic exercise on local cutaneous thermal hyperaemia.

Little is known about the acute changes in cutaneous microvascular function that occur in response to exercise, the accumulation of which may provide the basis for beneficial chronic cutaneous vascular adaptations. Therefore, we examined the effects of acute exercise on cutaneous thermal hyperaemia. Twelve healthy, recreationally active participants (11 male, 1 female) performed 30-minute cycling at 50 % (low-intensity exercise, LOW) or 75 % (high-intensity exercise, HIGH) maximum heart rate. Laser Doppler flowmetry (LDF) and rapid local skin heating were used to quantify cutaneous thermal hyperaemia before (PRE), immediately following (IMM) and 1-h (1HR) after exercise. Baseline, axon reflex peak, axon reflex nadir, plateau, maximum skin blood flow responses to rapid local heating (42 °C for 30-min followed by 44 °C for 15-min) at each stage were assessed and indexed as cutaneous vascular conductance [CVC = flux / mean arterial blood pressure (MAP), PU·mm Hg-1], and expressed as a percentage of maximum (%CVCmax). Exercise increased heart rate (HR), MAP and skin blood flow (all P < 0.001), and to a greater extent during HIGH (all P < 0.001). The axon reflex peak and nadir were increased immediately and 1-h after exercise (all comparisons P < 0.01 vs. PRE), which did not differ between intensities (peak: P = 0.34, axon reflex nadir: P = 0.91). The endothelium-dependent plateau response was slightly elevated after exercise (P = 0.06), with no effect of intensity (P = 0.58) nor any interaction effect (P = 0.55). CONCLUSION: Exercise increases cutaneous microvascular axonal responses to local heating for up to 1-h, suggesting an augmented sensory afferent function post-exercise. Acute exercise may only modestly affect endothelial function in cutaneous microcirculation.

Angiogenic potential is reduced in skeletal muscle of aged women.

KEY POINTS: The risk of cardiovascular disease and associated skeletal muscle microvascular rarefaction is enhanced in women after menopause, yet knowledge about the angiogenic potential in ageing women is generally sparse. Aged healthy and sedentary women were found to present a markedly impaired capacity for proliferation of skeletal muscle derived microvascular endothelial cells compared to young women. Vascular endothelial growth factor (VEGF) levels in skeletal muscle myocytes and release of VEGF from myocytes tended to be lower in aged compared to young women. The aged women did not show a detectable increase in skeletal muscle capillarization with 8 weeks of intense aerobic cycle training. Combined, the findings indicate that aged women have a reduced potential for capillary growth in skeletal muscle which, with ageing, may lead to age-induced microvascular rarefaction. ABSTRACT: Skeletal muscle angiogenic potential was examined in cell cultures derived from aged and young women, and the effect of 8 weeks of intense cycle training on muscle capillary growth was determined in the group of aged women. Basal muscle samples were obtained from healthy sedentary aged (n = 12; 64 ± 4.2 years) and young women (n = 5; 24 ± 3.2 years) for endothelial cell and skeletal muscle myocyte isolation and experiments. In addition, the aged women completed an 8-week training intervention. Peak oxygen uptake and muscle samples for histology and protein determination were obtained before and after the training period. Before training, muscle microdialysate was collected from the aged women at rest and during exercise. In Part 1 of the experiments, growth-supplement stimulated proliferation of endothelial cells was ∼75% lower in cells from aged compared to young women (P < 0.001). There was a tendency for a lower vascular endothelial growth factor (VEGF) concentration in muscle conditioned media (P = 0.0696) and for a lower VEGF content in the myocytes (P = 0.0705) from aged compared to young women. Endothelial proliferation was found to be highly dependent on mitochondrial function. Acute exercise resulted in a modest (1.3-fold; P = 0.0073) increase in muscle interstitial VEGF protein in the aged women. In Part 2, 8 weeks of intense training did not change muscle capillarization (P ≥ 0.1502) in the aged women, but led to an increased amount of muscle VEGF (P = 0.0339). In conclusion, aged women have impaired angiogenic potential, which is associated with a compromised response both at the skeletal muscle myocyte and microvascular endothelial cell level.

Antiprotozoal activity of 3'-deoxyinosine. Inverse correlation to cleavage of the glycosidic bond.

Two nucleosides related to the known antiprotozoal agent 1-(beta-D-ribofuranosyl)-1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidine-4-one (allopurinol riboside, 1) were prepared and evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma gambiense. 3'-Deoxyinosine (2) exhibited potent antiprotozoal activity against the three protozoal pathogens with minimal toxicity for host cells. It was found to be especially effective against the Columbia strain of T. cruzi reported to be resistant to 1. The antiprotozoal activity of 2 appeared to be inversely related to the rate of cleavage of the glycosidic bond, as shown by metabolic profiles of 2 in the various pathogenic hemoflagellates and host cells. Combining the key structural elements of 1 and 2 led to the synthesis of 1-(3-deoxy-beta-D-erythro-pentofuranosyl)-1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-one (3'-deoxy-allopurinol riboside, 3). which was found to be inactive as an antiprotozoal agent.