Angiotensin II increases protein synthesis in the rat heart

J Moi Cell Cardiol 24 (Supplement III) (1992) P73 NOREPINEPHRINE REGULATES DHP-RECEPTOR MESSAGE IN RAT CARDIAC MYOCYTES Tiina Maki, E. James Gruver, Darlene Toupin, Andrew R. Marks, James D. Marsh. Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. Isoproterenol has been shown to down-regulate and sympathetic innervation has been shown to up-regulate dihydropyridine-receptor (DHZP-R) expression in cultured cardiac myocytes. To clari@ the underlying mechanisms we studied the effects of norepinephrine (NE) on DHP-R mRNA levels in cultured cardiac myocytes isolated from 2-day old rats. Cells were grown in serum-free medium. Total RNA was isolated as described b!y Chomczynski. Northern blots were hybridized with a =P-labeled 1.3 kb cDNA probe for rat cardiac DHP-R, and results were quantified by laser densitometry. NE (1u9dM) induced a 30-80% decrease in DHP-R mRNA levels with an apparent maximum effect at lOa M. Decrease in mRNA was evident after 4 h and persisted for 48 h. A 70% reduction of DHPR mRNA could be induced also by phenylephrine (24 h, 10d M). Conversely, preliminary data show an initial 50% increase in DHP-R mRNA after 2 h with lO& M NEL Conclusion: NE regulates DHP-R mRNA in a biphasic concentration-dependent, and a biphasic temporal pattern. This pattern is at least partially a-receptor mediated, and may be modulated by homologous regulation of a-adrenergic receptors.

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ANGIOTRNSIN II INCRJXASBS PROTRIN SYNTRRSIS IN THE RAT HEART David L. Geenen, Ashwani Malhotra, Deren Liang, Atmaram Yarlaggada, James Scheuer . Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10467 USA. To demonstrate a direct effect of angiotensin II (AII) on cardiac muscle, Alzet pumps with saline (S;n=5) or non-hypertensive doses of .A11 (n=5) (3 pg/kg/hr) were implanted in rats with heterotopically transplanted hearts (TH). One week later, awake animals were infused with jH-leucine to measure total cardiac protein synthetic rate (Rs)., S AI1 m LV Weight (mg) 3ly5) 2513)“” 3$&) ';$;2' LV Protein (mg) 38(2) 26(2)** 6.04(0.51) 6.81(1.00) 6.15(0.35) 8.52(0.50)' KS (%I 2.28(0.29) 1.41(0.07)* 2.67(0.32) 2.19(0.18)# Rs (w/day)Data are X(SEM). NH, Native Heart; LV, Left Ventricle; KS, Fractional Synthesis; *P < 0.05 TH S vs NH S; **P < 0.05 TH AI1 vs NH AII; 'P < 0.05 TH AI1 vs TH S. In non-hypertensive doses, AI1 attenuates atrophy in the TH by directly stimulating protein synthesis.

p75 CARDIAC GROWTH FACTOR IN HYPERTROPHIED HEARTS OF RATS Makoto Nagano, Tohru Arino, Masahito Tsuchiya. Department of Medicine, The Jikei University School of Medicine, Tokyo/Japan

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This study was taken to verify the role of cardiac growth factor in hypertrophied rat hearts. For this purpose the hypertrophied hearts of Goldblatt hypertension type I and type II rats and those of normal rats were used. The supernatants of homogenized heart muscles were separated using an isoelectric focusing electrophoretic method to get a fraction with isoelectric point 8.3. This fraction was furthermore chromatographied using a HPLC method and was separated into 6 subfractions. We examined the cardiac growth effect of these isolated subfractions with cultured chicken embryonic cardiac myocytes. If the hearts were overloaded due to hypertension, a protein with a molecular weight 43 k dalton with isoelectric point 8.3 appeared and this protein induced the cardiac size. This protein appeared much later than proto-oncogenes and could be proved maximum at 5-6 weeks after beginning of the cardiac overload and than decreased gradually. This protein had no influence on the growth of body weight. s.29