Parathyroid hormone-related protein is rapidly up-regulated in blood vessels of rat skeletal muscle by low-frequency stimulation

Abstract.

To identify early changes in gene expression of fast-twitch rat muscle exposed to chronic low-frequency stimulation, differential display was applied comparing mRNA patterns between control and 12-h stimulated tibialis anterior (TA) muscles. Among the signals of differentially expressed mRNAs, a cDNA of ~300 bp was identified as specific to the parathyroid-hormone-related protein (PTHrP). As verified by semiquantitative reverse transcriptase polymerase chain reaction, this mRNA was present at low levels in normal slow-twitch soleus and fast-twitch TA muscles, but was ~80-fold elevated in TA muscles after 12 h of low-frequency stimulation. With ongoing stimulation for 2 or 4 days PTHrP mRNA returned to basal levels. PTHrP was located exclusively in blood vessels of both control and stimulated muscles. PTHrP immunohistochemistry revealed enhanced capillarization in 8-day stimulated muscles. In view of its vasodilative effect the up-regulation of PTHrP could be an important initial step related to enhanced capillarization in response to increased contractile activity.