The efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases.
This study was performed to investigate the effect of training under simulated hypoxic conditions. Hypoxia training was integrated into the normal training schedule of 12 endurance trained cyclists. Athletes were randomly assigned to two groups and performed three additional training bouts per week for six weeks on a bicycle ergometer. One group (HG) trained at the anaerobic threshold under hypoxic conditions (corresponding to an altitude of 3200 m) while the control group (NG) trained at the same relative intensity at 560 m. Preceding and following the six training weeks, performance tests were performed under normoxic and hypoxic conditions. Normoxic and hypoxic .VO2max, maximal power output as well as hypoxic work-capacity were not improved after the training period. Testing under hypoxic conditions revealed a significant increase in oxygen saturation (SpO 2, from 67.1 +/- 2.3 % to 70.0 +/- 1.7 %) and in maximal blood lactate concentration (from 7.0 to 9.1 mM) in HG only. Ferritin levels were decreased from 67.4 +/- 16.3 to 42.2 +/- 9.5 microg/l (p < 0.05) in the HG and from 54.3 +/- 6.9 to 31.4+/- 8.0 microg/l (p = 0.17) in the NG. Reticulocytes were significantly increased in both groups by a factor of two. In conclusion, the integration of six weeks of high intensity endurance training did not lead to improved performance in endurance trained athletes whether this training was carried out in hypoxic or normoxic conditions.
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