Regulation of the Renal Endothelin System in the Two-Kidney, One Clip Renal Hypertensive Rat

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Summary: Renovascular hypertension in the two-kidney, one clip (2K1C) model is characterized by initially elevated angiotensin-II (A-II) plasma concentrations, caused by ischemia in the clipped kidney and shear stress in the nonclipped kidney. These features are known stimuli of the endothelin (ET) system. The aim of this study was to analyze whether the renal ET system is activated in 2K1C renal hypertension in the rat. Wistar Kyoto rats (9 weeks old) were randomly assigned to four groups. Groups 1 and 3 underwent renal artery clipping, groups 2 and 4 were sham-operated. Groups 1 and 2 were used for analysis at 10 days after clipping, groups 3 and 4 12 weeks after clipping. We measured immunoreactive ET-1 renal tissue concentration as well as the ETA- and ETB-receptor density and affinity in renal cortex and medulla. We detected an increased immunoreactive ET-1 tissue concentration compared to the sham-operated control in the renal cortex of the nonclipped kidney 10 days (25.6 ± 12.0 pg/g vs 12.5 ± 5.0, 1 pg/g; p < 0.05) and in the renal cortex of the clipped kidney 90 days after clipping (92.4 ± 47 pg/g vs 22.9 ± 21 pg/g; p < 0.05). An increased ETA-receptor density was revealed in the renal medulla of the clipped kidney 10 days (624 ± 130 fmol/mg vs 276 ± 68 fmol/mg; p < 0.05) and 90 days (859 ± 131 fmol/mg vs 493 ± 93 fmol/mg; p < 0.05) after clipping. There were no differences in ETB-receptor density or binding affinity of either ETA- or ETB-receptors. In the 2K1C rat model of renovascular hypertension the renal ET system is activated. This activation is time-dependent and also dependent on the specific pathophysiological condition (clipped vs nonclipped). Increased ET-1 tissue concentration and upregulation of ETA-receptor density might lead to a synergistic activation of the ET system.