Upregulation of intracardiac adrenomedullin and its receptor system in rats with volume overload-induced cardiac hypertrophy.
Specific adrenomedullin receptors have been identified as calcitonin receptor-like receptor (CRLR)/receptor activity-modifying proteins (RAMP2 and RAMP3) complexes. Although we have demonstrated that adrenomedullin is increased in volume overload-induced cardiac hypertrophy, it remains unknown whether the adrenomedullin receptor is altered or not. This study sought to investigate the significance of intracardiac adrenomedullin and its receptor system in volume overload-induced cardiac hypertrophy. Left ventricular adrenomedullin levels were higher in aortocaval shunt (ACS) rats than in controls (+58%). The left ventricular gene expressions of adrenomedullin, CRLR, RAMP2 and RAMP3 were increased (+27%, +76%, +108% and +131%, respectively) and the left ventricular collagen gene expressions were also increased (type I: +138%, type III: +87%). The left ventricular adrenomedullin level correlated with the gene expression of type III collagen (R=0.42). These results suggest that intracardiac adrenomedullin and its receptor system are upregulated and may participate in the regulation of cardiac remodeling in volume overload-induced cardiac hypertrophy.
Yoshihara
Fumiki
F
Division of Hypertension and Nephrology, National Cardiovascular Center, Fujishirodai, Suita, Osaka 565-8565, Japan. fyoshi@ri.ncvc.go.jp
Nishikimi
Toshio
T
Okano
Ichiro
I
Hino
Jun
J
Horio
Takeshi
T
Tokudome
Takeshi
T
Suga
Shin-ichi
S
Matsuoka
Hiroaki
H
Kangawa
Kenji
K
Kawano
Yuhei
Y
D053607:Adrenomedullin; D000818:Animals; D058286:Calcitonin Receptor-Like Protein; D002306:Cardiac Volume; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic; D015854:Up-Regulation; D020257:Ventricular Remodeling
D058286:Calcitonin Receptor-Like Protein; D024061:Collagen Type III; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D020033:Protein Isoforms; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D053607:Adrenomedullin