MYOCARDIAL EXPRESSION OF ATRIAL-NATRIURETIC-FACTOR GENE IN EARLY STAGES OF HAMSTER CARDIOMYOPATHY

Ventricular cardiomyocytes represent the most important source of atri al natriuretic factor (ANF) in pathological conditions such as congest ive heart failure (CHF). It has been suggested that in cardiomyopathic Syrian hamster ventricles the ANF gene can be reactivated during the hypertrophic stage occurring before heart failure. The present study w as undertaken to investigate ANF gene expression during early stages o f myocardial damage and its distribution throughout atrial and ventric ular myocardium in UM-X7.1 cardiomyopathic Syrian hamsters (CMPH) befo re hypertrophy and cardiac failure occur. Atria, right and left ventri cles, and interventricular septum of hearts of 20-23 days old (young) and 90-95 days old (adult) CMPH were studied. The absence of hypertrop hy and cardiac failure was preliminarly ascertained by microscopic and hemodynamic evaluation. ANF-mRNA as well as tissue and plasma immunor eactive ANF were assayed. Moreover, ANF secretion pattern was evaluate d by immunocytochemical techniques. Young and adult CMPH hearts were i n the necrotic stage of myocardial disease, as demonstrated by histopa thological evaluation and by decreased wet weights (mg/g body weight) of different heart regions. Hemodynamic assessment showed no significa nt changes of left ventricular end-diastolic pressure (LVEDP) and a de crease of the left ventricular peak systolic pressure (LVSP) and + dP/ dt. Plasma immunoreactive ANF (IR-ANF) levels were higher in young (3- fold) and adult (6-fold) CMPH than in age-matched normal hamsters. A r educed IR-ANF concentration (per milligram protein) was observed in bo th young and adult cardiomyopathic atria in respect to healthy control s, whereas a higher IR-ANF concentration was present in ventricles. A 3-fold, 6-fold and 20-fold increase of IR-ANF concentration was found in right ventricular free-wall (RV), left ventricular free-wall (LV) a nd interventricular septum (IVS), respectively. Northern-blot analysis confirmed that IVS was the major site of ventricular ANF-mRNA transcr iption in both young and adult CMPH. ANF-mRNA was increased also in at ria where a faster peptide secretion can be hypothesized to lower tiss ue IR-ANF concentration. ANF secretion in ventricular myocardium was a chieved via constitutive pathway as demonstrated by immunocytochemistr y. Different patterns of ANF gene reactivation occur in CMPH myocardiu m before intraventricular pressure increases and structural hypertroph ic modifications are detectable. The extent of ANF gene reactivation i n CMPH ventricles parallels the severity of necrotic damage. Moreover, ANF gene expression is heterogeneously distributed throughout the myo cardium, suggesting that interventricular septum, the ontogenically yo ungest heart region, might preserve foetal characters which can be rap idly reactivated in pathological conditions.