The Effect of Combination Treatment with Angiotensin Converting Enzyme Inhibitor & Angiotensin II Receptor Blocker on the Apoptosis in the Kidney and on the MAP of Spontaneously Hypertensive Rats

Tak, Woo Taek; Yoon, Sung Chul; Kim, Yong Jin

Abstract

BACKGROUND
Either of the angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) has been known to be effective on the inhibition of progressive renal disease. The ACEI can cause angiotensin-II to be decreased, but make an plasma activity of renin and kinin to be increased. The ARB increase both activities of renin and angiotensin-II, while it block the function of angiotensin-II on the AT-1 receptor. This kind of process might influence on the activation of AT-2 receptor and lead to the activated state of antiproliferative change. Therefore, if the ARB and ACEI are treated at same time, that is, on the condition that angiotensin-II is somewhat suppressed and AT-1 receptor is blocked, this is strongly assumed to make the more positive effect on the inhibition of renal progression and hypertension control. METHODS: Experimental animals were chosen as a Spontaneously Hypertensive Rat (SHR) and a Wistar Kyoto Rat (WKR). Used total number were 32, including 11 (SHR 5, WKR 6) as a control. The other 21 SHR were allocated to pharmacy treated 3 groups (7 in each group as an ACEI treat, ARB treat, ACEI and ARB combination treat). The study on these animals was built by an observation on the BP, histopathologic change, the apoptosis & PCNA, the expression of AT-1 and AT-2 receptor. RESULTS: The mean arterial blood pressure (MAP) of SHR of a 5-month age was 153.2+/-3.4 mmHg, which was significantly high as compared to the control, 121.1+/-18.0 mmHg (p<0.01). The average of MAP in treated groups, 125.1+/-24.6 mmHg, was significantly decreased, as compared to untreated animals, 167.3+/-14.1 mmHg (p<0.01). The MAP in combination treatment animals is significantly lower than either of treatment group (p<0.05). The apoptotic process at the proximal tubule was observed less in case of treated animals, but the difference among treated 3 groups was not confirmed. CONCLUSION: The MAP decreasing effect by the combination treatment with ACEI and ARB was significant, however, the additive effect by this treatment on the inhibition of renal damage progression was not observed.