Vasopressin accelerates protein synthesis in neonatal rat cardiomyocytes.
Arginine vasopressin (AVP) has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia of fibroblasts. The present study examines the effect of AVP and endothelin-1 (ET-1) on protein, DNA, and RNA synthesis in primary cultures of serum deprived neonatal rat cardiomyocytes (RC) as assessed by changes in [3H] phenylalanine, [3H] thymidine, and [14C] uridine incorporation respectively. Both AVP and ET-1 evoked significant increases in protein synthesis in RC of 36 +/- 12% (p < 0.05) and 53 +/- 22% (p < 0.01) respectively. The stimulating action of AVP on [3H] phenylalanine incorporation was abolished by pretreatment with 2-nitro-4carboxyphenyl-N, N-diphenylcarbamate (NCDC), a phospholipase C (PLC) inhibitor. [14C] uridine incorporation was significantly higher in cells incubated with ET-1 (95 +/- 12%) but not AVP (9 +/- 11%). Neither AVP nor ET-1 significantly affected cell number or [3H]thymidine incorporation, suggesting a lack of a hyperplastic effect. AVP evoked an increase in [Ca2+]i levels (162 +/- 12 nmol/L from a basal value of 77 +/- 6 nmol/L) which was completely abolished by pretreatment with either NCDC or cyclopiazonic acid (sarcoplasmic reticulum (SR) Ca2+ pump inhibitor) but unaffected by ryanodine (ryanodine sensitive SR Ca2+ store depletor). Taken together, these data suggest that AVP, in a PLC dependent manner, both stimulates protein synthesis and augments [Ca2+]i release in RC from ryanodine insensitive (IP3 sensitive) Ca2+ stores. Thus, AVP may promote cardiac hypertrophy via direct effects on cardiomyocyte protein synthesis secondary to IP3 mediated [Ca2+]i release.
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Y
Y
Xu
R L
RL
Hopfner
J R
JR
McNeill
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V
Gopalakrishnan
D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010452:Peptide Biosynthesis / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D010455:Peptides; D014316:Tritium; D001127:Arginine Vasopressin; D010649:Phenylalanine; D002118:Calcium