SummaryVitamin E (VE) deficiency is accompanied by myopathy in various animal species including man. Although gene expression profiles related to degenerative and regenerative processes in different kinds of myopathies have been studied, no global expression profile for skeletal muscle subject to VE deficiency has previously been reported. In the present study, Affymetrix GeneChip 1 technology was used to obtain such a profile. Two groups of male rats were fed with either a diet deficient in VE or a control diet. Differential gene expression was monitored at five timepoints over 430 days, with all animals individually profiled. Out of *7000 genes represented on the Genechip, 56 were found to be upregulated in response to VE deficiency in at least four consecutive time-points from as early as 91 days of deficiency. Up-regulated genes included muscle structure and extra cellular matrix genes, as well as anti-oxidative, anti-inflammatory and anti-fibrotic genes. Our data show that molecular transcription might provide a very early marker to detect oncoming degenerative conditions in VE deficiency. They provide further insight into possible molecular mechanisms underlying VE deficiency in skeletal muscle, and reveal the activation of an intensive protection program that can explain the long maintenance of muscle structure during deficiency.

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The height of the dicrotic notch between the systolic and diastolic peaks of the peripheral pulse wave, expressed as a fraction of the overall amplitude of the wave, is sensitive to nitric oxide (NO) bioactivity. This phenomenon might form the basis of a simple, non-invasive method for determining endothelial function in vivo. We assessed whether the phenomenon is specific to the NO pathway or whether other vasoactive agents have similar effects. The relative height of the dicrotic notch (RHDN) was determined by photoplethysmography in the rabbit ear. It was dose-dependently decreased by acetylcholine, a stimulator of endothelial NO synthesis, and increased by N G -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. There was no effect on RHDN of the α-adrenergic blocker phentolamine or the β-adrenergic blocker propranolol. The cyclo-oxygenase inhibitor indomethacin dose-dependently decreased RHDN but this effect was blocked by L-NAME, suggesting it was mediated by cross-talk with the NO pathway. Changes in RHDN appeared to be independent of heart rate and of the delay between the systolic peak and the notch, but were associated with changes in the slope of the dicrotic limb. Both L-NAME and phentolamine produced multiple diastolic peaks, indicative of wave reflections in the vasculature. These data support the view that changes in RHDN are specific to the NO pathway and provide additional information about the mechanisms involved.