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 examine s the effect of AVP and endothelin-1 (ET-1) on protein, DNA, and RNA synthe sis in primary cultures of serum deprived neonatal rat cardiomyocytes (RC) as assessed by changes in [H-3] phenylalanine, [H-3] thymidine, and [C-14] uridine incorporation respectively. Both AVP and ET-1 evoked significant in creases in protein synthesis in RC of 36 +/- 12% (p < 0.05) and 53 +/- 22% (p < 0.01) respectively. The stimulating action of AVP on [H-3] phenylalani ne incorporation was abolished by pretreatment with 2-nitro-4carboxyphenyl- N,N-diphenylcarbamate (NCDC), a phospholipase C (PLC) inhibitor. [C-14] uri dine incorporation was significantly higher in cells incubated with ET-1 (9 5 +/- 12%) but not AVP (9 +/- 11%). Neither AVP nor ET-1 significantly affe cted cell number or [H-3] thymidine incorporation, suggesting a lack of a h yperplastic 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 abolishe d by pretreatment with either NCDC or cyclopiazonic acid (sarcoplasmic reti culum (SR) Ca2+ pump inhibitor) but unaffected by ryanodine (ryanodine sens itive SR Ca2+ store depletor). Taken together, these data suggest that AVP, in a PLC dependent manner, stimulates both protein synthesis and augments [Ca2+](i) release in RC from ryanodine insensitive (IP3 sensitive) Ca2+ sto res. Thus, AVP may promote cardiac hypertrophy via direct effects on cardio myocyte protein synthesis secondary to IP3 mediated [Ca2+](i) release.