SERUM FROM PATIENTS WITH CHRONIC RENAL-INSUFFICIENCY ALTERS GROWTH-CHARACTERISTICS AND ANP MESSENGER-RNA EXPRESSION OF ADULT-RAT CARDIAC MYOCYTES

Left ventricular hypertrophy is very prevalent among patients with ren al insufficiency. Known hypertrophic factors, such as systemic hyperte nsion, do not adequately account for the prevalence of left ventricula r hypertrophy in these patients. Circulating growth factors may stimul ate cardiomyocyte growth and contribute to the development of left ven tricular hypertrophy. The effects of sera from patients with (n=30) an d without (n=5) chronic renal insufficiency on the growth of cultured adult cardiomyocytes were compared. An adult rat cardiomyocyte primary culture system was established with a high purity of cardiomyocyte po pulation as confirmed by immunocytochemical staining of cardiac contra ctile proteins, Myocytes responded with increased [H-3]thymidine incor poration when treated with angiotensin II, epidermal growth factor, hy drocortisone and insulin, and with increased [H-3]phenylalanine incorp oration when treated with parathormone, isoproterenol, phenylephrine a nd insulin, Renal insufficiency serum stimulated [H-3]thymidine incorp oration was 1.5 times that of the control (P<0.02) and also tended to increase incorporation of [H-3]phenylalanine compared to the control ( P=N.S.). Increased [H-3]thymidine incorporation by renal insufficiency serum did not correlate with serum insulin, parathormone or glucose i n the renal insufficiency patients. A quantitative reverse transcripta se polymerase chain reaction (RT-PCR) method was used to measure renal insufficiency serum-induced atrial natriuretic peptide mRNA expressio n in cultured cardiomyocytes. Atrial natriuretic peptide (ANP) mRNA wa s increased 1-3-fold in cardiomyocytes treated with renal insufficienc y sera in comparison to control sera. These data suggest that circulat ing growth factor(s) may contribute to the development of cardiac hype rtrophy in patients with renal insufficiency. (C) 1996 Academic Press Limited