Effects of Renin—Angiotensin System Inhibition on Cardiac Hypertrophy and Fibrosis in Spontaneously Hypertensive Rats

Abstract

The present study examined whether the inhibition of the renin-angiotensin system can change the cardiac remodeling process in spontaneously hypertensive rats (SHR). First, we administered AT1, blockade (losartan), AT2 blockade (PD123319), or ACE inhibitor (enalapril) to SHR from 10 to 20 weeks of age. Both losartan and enalapril reduced the arterial systolic blood pressure (BP) as well as the collagen concentration compared with the untreated SHR (U-SHR) to the level of Wistar Kyoto rats (WKY). Both agents also reduced both the left ventricular (LV) weight and the ratio of LV to body weight (BW) compared with the untreated SHR, although these measures were still larger than those of WKY. However, PD123319 was without effect. Second, to inhibit the plasma angiotensinogen (ATN) in SHR, we intravenously injected antisense oligodeoxynucleotides (ODNs) against rat ATN coupled to asialoglyco-protein carrier molecules into SHR (A-SHR) from 10 to 20 weeks via their tail veins twice a week. Both the ATN and Ang II concentrations in plasma decreased in A-SHR compared with those of the sense-treated SHR (S-SHR) or U-SHR. The BP in A-SHR was reduced in comparison with those of S-SHR or U-SHR, although BP in A-SHR was still higher than that in WKY. Both LV weight and the ratio of LV to BW also decreased in A-SHR compared with S-SHR or U-SHR. No difference in the LV collagen concentrations was observed among all SHR groups. These findings showed that ATN inhibition, ACE, and AT1 blockade could reduce the hypertrophy of myocytes in SHR. However, since the partial BP reduction did not produce changes in the remodeling of matrix tissue, it may be that both the reduction of BP and the inhibition of RAS play a crucial role in cardiac hypertrophy in SHR.