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 previously been implicated in the development of cardiac hypertrophy. We therefore investigated the role of CGRP in pressure overload-induced hypertrophy in vivo, which has not previously been reported. Constriction of the ascending aorta of rats resulted in an increase in the heart weight to body weight ratio, increased myocyte diameter, re-expression of the fetal genes ANF, MHCbeta and skeletal alpha-actin, and decreased expression of the adult genes GLUT4 and SERCA2a. Treatment of neonatal rat pups (1-2 days old) with capsaicin (50 mg/kg), resulted in the permanent de-afferentation of small-diameter unmyelinated CGRP-containing sensory C-fibres. Such treatment caused a 68% decrease in the CGRP-like immunoreactivity of hearts isolated from 10 week old rats (p < 0.001). Contrary to expectations, aortic constriction of capsaicin treated rats had no effect on the development of hypertrophy at the trophic, morphometric or gene expression levels. The results suggest that the development of pressure overload-induced hypertrophy in vivo does not require the regulatory neuropeptide CGRP.
Young
M E
ME
Department of Internal Medicine, University of Texas-Houston Medical School, 77030, USA.
Okerberg
K A
KA
Wilson
C R
CR
Deferrari
D A
DA
Ying
J
J
Guthrie
P
P
Razeghi
P
P
Clubb
F J
FJ
Taegtmeyer
H
H
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D051275:Glucose Transporter Type 4; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D000199:Actins; D051275:Glucose Transporter Type 4; D015395:Histocompatibility Antigens Class I; C098080:MICB antigen; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin