Inhibitory regulation of hypertrophy by endogenous atrial natriuretic peptide in cultured cardiac myocytes.
Atrial natriuretic peptide (ANP) may function as an endogenous regulator of cardiac hypertrophy, because the natriuretic peptide receptor has been found in the heart and because mice lacking its receptor have been shown to have a markedly elevated ventricular mass. We examined the role of endogenous ANP in cardiac hypertrophy in vitro. The effects of the blockade of endogenous ANP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated with the use of cultured neonatal rat ventricular myocytes. HS-142-1 increased the basal and phenylephrine (PE, 10(-5) mol/L)-stimulated protein syntheses in a concentration-dependent manner (1 to 300 microg/mL). A significant increase in the cell size of myocytes was also induced by this antagonist. In addition, the expression levels of skeletal alpha-actin, beta-myosin heavy chain, and ANP genes, markers of hypertrophy, were partially elevated by treatment with HS-142-1 (100 microg/mL) under nonstimulated or PE-stimulated conditions. A cGMP-specific phosphodiesterase inhibitor, zaprinast (5x10(-4) mol/L), and a cGMP analogue (10(-4) mol/L) suppressed the basal and PE-stimulated protein syntheses. Our observations suggest that endogenous ANP inhibits cardiac myocyte hypertrophy under basal and PE-stimulated conditions, probably through a cGMP-dependent process. ANP may play a role as an autocrine factor in the regulation of cardiac myocyte growth.
Horio
T
T
Division of Hypertension, Department of Medicine, National Cardiovascular Center, Suita, Osaka, Japan. thorio@jsc.ri.ncvc.go.jp
Nishikimi
T
T
Yoshihara
F
F
Matsuo
H
H
Takishita
S
S
Kangawa
K
K
D000199:Actins / Q000235:genetics; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D020097:Natriuretic Peptide, Brain; D010656:Phenylephrine / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D000199:Actins; C072551:HS 142-1; D011134:Polysaccharides; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains