Altered sympathetic system and adrenoceptors during the development of cardiac hypertrophy

Increasing experimental evidence suggests that the development of cardiac hypertrophy may involve the sympathetic system and associated receptor mechanisms. However, very little work has been done so far to understand changes in the sympathetic system and cardiac adrenoceptors soon after an increased work load is imposed on the heart. Accordingly rat hearts subjected to aortic banding-induced pressure overload were assessed 3, 7, and 14 days postoperatively. Sham-operated rats without aortic banding were used as a control group. Rats with aortic constriction had increases in heart rate, left ventricular systolic pressure, and total mechanical energy during the entire study period. The cardiac RNA level was increased without a significant increase in left ventricular mass on days 3 and 7 in aortic-banded animals; these results were associated with a decrease in the cardiac norepinephrine (NE) store and an increase in the plasma level of NE and dopamine β-hydroxylase (DBH) activity. By day 14 a significant increase in left ventricular mass and the NE store were found; both plasma NE and DBH remained elevated. Catecholamines in other tissues such as the spleen and kidney were depleted in the banded group, whereas the dopamine level, particularly in the brain, was signficantly higher during the entire study. Furthermore, the density of α-adrenoceptors was higher on day 3 of aortic banding, and a reciprocal correlation was evident between cardiac α- and β-adrenoceptors on day 14; the density of β-adrenoceptors was increased, whereas that of α-adrenoceptors was decreased in the banded group. These results indicate a generalized increase in sympathetic activity at the initial stages after an increased work load is imposed on the heart and support the view that both catecholamines and adrenoceptors contribute significantly to the development of cardiac hypertrophy.