Altered cardiac polyamine biosynthesis in spontaneously hypertensive rats

Abstract

To evaluate the role of polyamine biosynthesis in myocardial growth, the activity of ornithine decarboxylase (ODC) and the levels of the polyamines, spermidine, spermine, and putrescine, were measured in the hearts of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats between birth and 30 wk of age and in 30-wk-old rats after 6 wk treatment with either minoxidil (0.08 mg/ml) or methyldopa (5 mg/ml drinking water). ODC activity was initially high in the developing heart (150 pmol X mg protein-1 X 30 min-1) and decreased with age. In the SHR after 4 wk of age, spermidine content was consistently raised in both ventricles compared with the WKY rats. Spermine was reduced in the left ventricle of the SHR, resulting in high spermidine-to-spermine ratios characteristic of rapidly growing systems. Ventricular ODC activity and putrescine levels were also slightly but less consistently elevated in the ventricles of the SHR compared with respective WKY rats. Minoxidil treatment increased heart weight and left ventricular spermidine and spermine content in both SHR and WKY rats. Methyldopa also caused a significant increase in left ventricular spermidine content despite a marked reduction in ventricular mass. Thus ventricular hypertrophy in SHR is accompanied by an enhanced synthesis and accumulation of spermidine. The fact that myocardial spermidine content increased during methyldopa treatment, which reduced the myocardial mass, suggests that regression of ventricular hypertrophy can occur independently of changes in polyamine content.