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

To identify early changes in gene expression of fast-twitch rat muscle expo sed to chronic low-frequency stimulation, differential display was applied comparing mRNA patterns between control and 12-h stimulated tibialis anteri or (TA) muscles. Among the signals of differentially expressed mRNAs, a cDN A of similar to 300 bp was identified as specific to the parathyroid-hormon e-related protein (PTHrP). As verified by semi-quantitative reverse transcr iptase polymerase chain reaction, this mRNA was present at low levels in no rmal slow-twitch soleus and fast-twitch TA muscles, but was similar to 80-f old elevated in TA muscles after 12 h of low-frequency stimulation. With on going stimulation for 2 or 4 days PTHrP mRNA returned to basal levels. PTHr P was located exclusively in blood vessels of both control and stimulated m uscles. PTHrP immunohistochemistry revealed enhanced capillarization in g-d ay stimulated muscles. In view of its vasodilative effect the up-regulation of PTHrP could be an important initial step related to enhanced capillariz ation in response to increased contractile activity.