Effects of captopril on the renin angiotensin system, oxidative stress, and endothelin in normal and hypertensive rats

Abstract

There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats.

Figure 1

Top panels show MAP (left), circulating levels of Ang II (center), and ET (right) in SD (genetically-unrelated controls; n=11), WKY (genetically related controls; n=5), and SHR (n=7). Bottom panels show PRA (left) and TBARS (right) in SD (n=4), WKY (n=6), and SHR (n=7). The SHR had higher MAP with parallel increases in Ang II and ET levels when compared with either SD or WKY (n=8, 6, and 8, for the SD, WKY, and SHR, respectively). In contrast, PRA and plasma TBARS levels in the SHR were similar to those of SD and WKY rats. *P<0.05 between the SHR values (n=7) and those from the SD (n=4) and WKY rats (n=6).

Figure 2

Top panels show MAP (left), plasma Ang II (center), and ET (right) in WKY and SHR that were either left untreated (□ open bars) or treated for 15 days with captopril (■ closed bars). Bottom panels show PRA (left) and TBARS (right) in untreated and captopril-treated WKY and SHR. Captopril treatment in SHR caused analogous decreases in MAP, Ang II, and ET in SHR, but had no discernable effects on these parameters in WKY. Likewise, captopril decreased TBARS only in the SHR. However, it increased PRA in both groups (confirming angiotensin-converting enzyme inhibition). P<0.05 from WKY rats; #P<0.05 from the corresponding untreated WKY or SHR rats. Number of animals (for untreated and captopril-treated WKY and SHR, respectively). MAP: n=5, 6, 7, and 7; Ang II: n=6, 6, 7, and 7; ET: n=6, 6,8, and 12; PRA: n=6, 6, 7, and 7; TBARS: n=5, 6, 7, and 7.