Calcitonin gene-related peptide is not essential for the development of pressure overload-induced hypertrophy in vivo

The regulatory neuropeptide calcitonin-gene related peptide (CGRP) has been shown to evoke a hypertrophic response in isolated cardiomyocytes in vitro , an effect which was attributed to PKC activation. Activation of PKC has p reviously been implicated in the development of cardiac hypertrophy. We the refore investigated the role of CGRP in pressure overload-induced hypertrop hy in vivo, which has not previously been reported. Constriction of the asc ending aorta of rats resulted in an increase in the heart weight to body we ight ratio, increased myocyte diameter, re-expression of the fetal genes AN F, MHC beta and skeletal alpha -actin, and decreased expression of the adul t genes GLUT4 and SERCA2a. Treatment of neonatal rat pups (1-2 days old) wi th capsaicin (50 mg/kg), resulted in the permanent de-afferentation of smal l-diameter unmyelinated CGRP-containing sensory C-fibres. Such treatment ca used a 68% decrease in the CGRP-like immunoreactivity of hearts isolated fr om 10 week old rats (p < 0.001). Contrary to expectations, aortic constrict ion of capsaicin treated rats had no effect on the development of hypertrop hy at the trophic, morphometric or gene expression levels. The results sugg est that the development of pressure overload-induced hypertrophy in vivo d oes not require the regulatory neuropeptide CGRP.