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Vasopressin accelerates protein synthesis in neonatal rat cardiomyocytes
Y Xu1, R L Hopfner, J R McNeill
1Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Insights
Arginine vasopressin (AVP) and endothelin-1 (ET-1) increase protein synthesis in cardiomyocytes. AVP stimulates protein synthesis via phospholipase C and calcium release, potentially promoting cardiac hypertrophy.
Area of Science:
- Cardiovascular Biology
- Cellular Physiology
Background:
- Arginine vasopressin (AVP) is known to induce vascular smooth muscle cell hypertrophy.
- The role of AVP in cardiomyocyte growth requires further elucidation.
Purpose of the Study:
- To investigate the effects of AVP and endothelin-1 (ET-1) on protein, DNA, and RNA synthesis in neonatal rat cardiomyocytes (RC).
- To explore the signaling pathways involved in AVP-induced cardiomyocyte responses.
Main Methods:
- Primary cultures of serum-deprived neonatal rat cardiomyocytes were used.
- Incorporation of [3H] phenylalanine, [3H] thymidine, and [14C] uridine assessed protein, DNA, and RNA synthesis, respectively.
- Intracellular calcium ([Ca2+]i) levels were measured, and the effects of specific inhibitors (NCDC, cyclopiazonic acid, ryanodine) were evaluated.
Main Results:
- Both AVP and ET-1 significantly increased protein synthesis in RC.
- AVP's effect on protein synthesis was dependent on phospholipase C (PLC) activity.
- ET-1, but not AVP, increased RNA synthesis.
- Neither AVP nor ET-1 affected cell number or DNA synthesis, indicating no hyperplastic effect.
- AVP increased intracellular calcium ([Ca2+]i) via IP3-sensitive stores, independent of ryanodine-sensitive stores.
Conclusions:
- AVP stimulates cardiomyocyte protein synthesis and increases intracellular calcium through a PLC-dependent mechanism involving IP3-sensitive stores.
- These findings suggest that AVP may directly promote cardiac hypertrophy by enhancing cardiomyocyte protein synthesis secondary to IP3-mediated calcium release.
Abstract:
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.