Different Levels of Hypertension Induce Opposite Diuretic Behaviors from the Nonclipped Kidney in the Rat Two-Kidney, One-Clip Model

Abstract

This study was carried out on conscious two-kidney, one-clip (2K1C) rats to establish whether different levels of hypertension induced opposite diuretic behaviors from the nonclipped kidney. Mildly hypertensive rats and severely hypertensive rats were produced by, respectively, constricting their right renal arteries with 0.3-mm and 0.15-mm clips. On the 11th day of the study, the systolic blood pressure (SBP) of the 0.3-mm clip rats was 150 ± 2 mm Hg, the water intake was 24 ± 1 ml, and the urine output was 7 ± 1 ml. The SBP of the 0.15-mm clip rats was 231 ± 10 mm Hg, the water intake was 46 ± 4 ml, and the urine output was 27 ± 6 ml. The data from the two groups are significantly different. On the 19th day half of the mildly hypertensive (0.3-mm clip) rats that received cilazapril from day 15 had, with respect to their water-treated counterparts, a SBP of 140 ± 8 as compared with 159 ± 7 mm Hg, the water intake was 37 ± 5 as compared with 26 ± 4 ml, and the urine output was 18 ± 4 as compared with 12 ± 1 ml. In contrast, half of the severely hypertensive (0.15-mm clip) rats that received cilazapril had, with respect to their water-treated counterparts, a SBP of 143 ± 4 as compared with 227 ± 10 mm Hg, the water intake was 30 ± 2 as compared with 51 ± 9 ml, and the urine output was 8 ± 2 as compared with 29 ± 4 ml. All changes induced by cilazapril are significant in both groups. The data of this study suggest that different levels of hypertension in the rat 2K1C model induce opposite water elimination modes from the nonclipped kidney. This conclusion is supported by the different shift in the water intake and urine output among the cilazapril-treated rats of the two groups. This contrast in the response to cilazapril seems to be dependent on the magnitude of the resulting hypotension. Thus, it seems that in this model, when the hypertension is mild, the antidiuretic effect of angiotension II on the nonclipped kidney is exhibited, whereas, when the hypertension is severe, the diuretic influence of the blood pressure is evident. Irrespective of these different characteristics of the submodels of 2K1C, angiotensin I converting enzyme inhibitors, such as cilazapril, are effective in normalizing the blood pressure.