Activation of angiotensinogen and angiotensin-converting enzyme gene expression in the left ventricle of senescent rats.

Abstract

During senescence, the plasma angiotensin II concentration is decreased, but the regulation of intracardiac angiotensin II synthesis has never been investigated. The purpose of this work was to determine the cardiac content of both angiotensinogen (ANG) and angiotensin-converting enzyme (ACE) mRNAs in 24-month-old Wistar rats. Total cardiac RNAs and known amounts of ANG and ACE mRNA transcripts, used as standards, were hybridized on slot blots with specific cDNA probes. The quantities of ANG and ACE mRNA were evaluated from the regression lines obtained with fragments of ANG and ACE mRNA in vitro transcripts. With aging, while the overall plasma renin-angiotensin system (RAS) activity decreased, in the left ventricle (LV) the amounts of ANG and ACE mRNAs were increased by fivefold (P < .01) and 2.5-fold (P < .01), respectively, compared with young adult controls. By contrast, in the right ventricle (RV) the same mRNA levels remained unchanged. In parallel, we also found an enhanced expression of the atrial natriuretic factor (ANF) in the LV but not in the RV. During senescence, the depressed circulating RAS activity is in contrast to the increase of both ANG and ACE mRNA levels in the LV. Such an upregulation in both gene activities is more likely to be related to the age-associated changes in arterial compliance rather than to hormonal changes, since (1) this regulation is found only in the LV and (2) the same pattern of regulation is also observed for the ANF mRNA level.