Summary
We investigated whether nitric oxide (NO) synthase gene transfer could attenuate α-adrenergic agonist-induced growth of cardiac myocytes. First, we investigated the effects of exogenous NO and a cGMP analogue on protein synthesis of cultured neonatal rat cardiac myocytes. The NO donor, morpholinosydnonimine (SIN-1), and 8-bromo-cGMP caused concentration-dependent decreases in phenylephrine (Phe)-induced 3H-leucine incorporation into myocytes. We then transferred endothelial NO synthase (eNOS) gene into cardiac myocytes using adeno-associated virus (AAV) vectors. eNOS gene transfer into cardiac myocytes induced 140 kDa eNOS protein expression and significantly increased cGMP contents of myocytes compared with control cells. eNOS gene transfer also inhibited 3H-leucine incorporation into cardiac myocytes in response to Phe, which was significantly recovered in the presence of the NOS inhibitor NG-monometyl-L-arginine acetate. These results indicate that authentic NO attenuates the effects of the α-adrenergic agonist-induced cardiac hypertrophy at least partially via cGMP production, suggesting that eNOS gene transfer using AAV vectors is promising for the gene therapy of cardiac hypertrophy.
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Ikeda, U. et al. (2000). Nitric Oxide Synthase Gene Transfer Inhibits Protein Synthesis of Rat Cardiac Mycocytes. In: Takeda, N., Nagano, M., Dhalla, N.S. (eds) The Hypertrophied Heart. Progress in Experimental Cardiology, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4423-4_33
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DOI: https://doi.org/10.1007/978-1-4615-4423-4_33
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