Vascular endothelial growth factor expression in heart of rats exposed to hypobaric hypoxia: differential response between mRNA and protein.

This study investigated the role of vascular endothelial growth factor (VEGF) in the neoangiogenesis induced in heart in response to hypoxia. The time-course of adaptive changes in capillary supply, expression of VEGF mRNA and protein was studied in right (RV) and left ventricles (LV) of rats exposed to hypobaric hypoxia during 1-25 days (barometric pressure = 505 hPa). VEGF mRNA levels encoding for VEGF 188 and 164 isoforms were measured by reverse transcription-polymerase chain reaction (RT-PCR) and VEGF protein was determined by Western blotting. Relative RV weight (i.e., weight of RV related to body weight) increased with hypoxia and was 102% higher than in controls after 15 days of exposure (P < 0.01), while relative LV weight remained unaltered. A rapid and transient increase in VEGF 188 mRNA occurred after 1 day of hypoxia in LV (P < 0.05). Thereafter, a delayed increase in VEGF 188 mRNA expression occurred in RV (ANOVA, P < 0.001). By day 18, VEGF 188 mRNA level was higher in hypoxic than in control rats (P < 0.005) and then decreased to base line levels. Hypoxia did not affect the expression of VEGF 164 mRNA neither in LV nor in RV. One of the main results was that these hypoxia-induced alterations in VEGF transcripts were not followed by associated increase in VEGF protein. These results suggest that capillary growth observed in RV after prolonged exposure to ambient hypoxia likely results from other molecular mechanisms than VEGF.

Exercise-induced expression of vascular endothelial growth factor mRNA in rat skeletal muscle is dependent on fibre type.

In this study, we quantified the expression of the vascular endothelial growth factor (VEGF) gene in individual muscle fibres at the end of a single 90 min run of 20-25 m min-1, at 10 % incline. In addition, we evaluated the co-ordinated expression of several hypoxia-sensitive genes, including the ORP-150 gene. Individual fibres were taken from rat plantaris muscle, either at the end of a single bout of exercise or at rest, and classified as Type I, IIa, IIx or IIb, according to the expression of myosin heavy chain (MHC) isoforms. VEGF mRNA levels increased by 90 % in exercising whole plantaris in comparison with those in control muscle (P < 0.001), while the VEGF protein content increased by 72 % (P < 0.05). Using real-time PCR analysis, an accurate and reproducible method for quantification of mRNA levels, a marked rise in VEGF transcript levels was observed at the end of exercise in individual myofibres (P < 0.05), providing the first direct evidence that VEGF transcripts increase in muscle cells after a single bout of exercise. This exercise-induced increase in VEGF transcript levels was specifically observed in type IIb myofibres, which are predominantly glycolytic and more susceptible to local hypoxia than oxidative myofibres such as type I or IIa fibres (110 %, P < 0.05). Moreover, treadmill exercise increased the expression of two hypoxia-sensitive genes. The levels of mRNA for Flt-1, a VEGF-specific receptor, and those for ORP-150, a chaperone essential for the secretion of mature VEGF, increased in whole plantaris muscles (108 and 92 %, respectively, P < 0.05). Taken together, these findings are consistent with the suggestion that hypoxia could be one of the mechanisms involved in exercise-induced capillary growth.

Over-stimulation of the vestibular system and body balance.

The purpose of this study was to examine whether an over-stimulation of the vestibular system, induced by thousands of time saccadic head stimulations, affects the vestibular sensitivity, and consequently if such a phenomenon could contribute to the deterioration of postural stability observed after a long distance running exercise. Eighteen athletic subjects performed a 20.5 km over ground race with an average speed of 15 km x h(-1), corresponding roughly to 7,500 strides shocks with associated saccadic accelerations transmitted to the head. A preliminary validation of the exercise protocol was realized to confirm the effect of the sustained exercise on body balance by recording standard postural parameters. A visually perceived eye level (VPEL) task was used to indirectly assess otolithic sensitivity motionless or undergoing low centrifugation conditions, before and after exercise. Results obtained from body balance analysis confirmed a decreased postural stability illustrated by increased postural oscillations after the 20.5 km run. Under low centrifugation conditions, results showed a lowering of the VPEL with the increase of the gravito-inertial acceleration in accordance with the literature. However, no significant change in the VPEL after a sustained running exercise was observed. In conclusion, the vestibular sensitivity at the otolithic level does not seem to be altered by an intensive running exercise and then failed to play a key role in the post-exercise deterioration of postural stability.