Patients with chronic renal failure (CRF) have impaired exercise capacity e
ven after erythropoietin treatment. We recently showed that although this i
s explained in part by reduced convective O-2 delivery to muscles, there is
also an impairment of O-2 transport from muscle capillaries to the mitocho
ndria. Given the importance of the capillary surface area for capillary mit
ochondrial O-2 transport and reports of reduced capillarity in CRF, we hypo
thesized that the angiogenic gene response to exercise is impaired in such
patients. Six patients with CRF and six control subjects matched for age, s
ize, and sedentary lifestyle exercised on a single occasion for 1 h at simi
lar work intensities averaging 50% of maximal capacity. Exercise was confin
ed to the knee extensors of a single leg by means of a specially designed l
eg-kick ergometer. A percutaneous biopsy of the quadriceps was taken within
30 min of cessation of exercise and compared with a similar biopsy done at
different times without any prior exercise for 24 h. Conventional Northern
blots were prepared and probed for vascular endothelial growth factor (VEG
F; the major putative angiogenic growth factor for muscle), basic fibroblas
t growth factor (bFGF), and transforming growth factor (TGF)-beta (1). Data
during both rest and exercise were successfully obtained in four subjects
of each group. We also assessed muscle capillarity and mitochondrial oxidat
ive capacity to relate to these changes. Mitochondrial oxidative capacity w
as normal, whereas capillary number per fiber was 12% lower than in normal
subjects. VEGF mRNA abundance was increased after exercise by about one ord
er of magnitude, with no reduction in response in CRF. For bFGF and TGF-bet
a (1), exercise elicited no response in either group. Reduced muscle capill
arity in CRF does not, therefore, stem from reduced transcription of VEGF.
To the extent that VEGF is important to exercise-induced angiogenesis in mu
scle, we suspect a posttranscriptional aberration in this response occurs i
n CRF to explain reduced capillarity.