Renin-angiotensin system and sympathetic nervous system in cardiac pressure-overload hypertrophy

Angiotensin II and norepinephrine (NE) have been implicated in the neurohum oral response to pressure overload and the development of left ventricular hypertrophy. The purpose of this study was to determine the temporal sequen ce for activation of the renin-angiotensin and sympathetic nervous systems in the rat after 3-60 days of pressure overload induced by aortic constrict ion. Initially on pressure overload, there was transient activation of the systemic renin-angiotensin system coinciding with the appearance of left ve ntricular hypertrophy (day 3). At day 10, there was a marked increase in AT (1) receptor density in the left ventricle, increased plasma NE concentrati on, and elevated cardiac epinephrine content. Moreover, the inotropic respo nse to isoproterenol was reduced in the isolated, perfused heart at 10 days of pressure overload. The affinity of the beta (2)-adrenergic receptor in the left ventricle was decreased at 60 days. Despite these alterations, the re was no decline in resting left ventricular function, beta -adrenergic re ceptor density, or the relative distribution of beta (1)- and beta (2)-rece ptor sites in the left ventricle over 60 days of pressure overload. Thus ac tivation of the renin-angiotensin system is an early response to pressure o verload and may contribute to the initial development of cardiac hypertroph y and sympathetic activation in the compensated heart.