The renal vascular response to ANG II injection is reduced in the nonclipped kidney of two-kidney, one-clip hypertension

Abstract

The ANG II receptor 1 (AT1R) level in the nonclipped kidney of two-kidney, one-clip hypertension (2K1C) has shown to be unchanged despite a high circulating angiotensin (ANG) II level. To examine the vasoreactive response to ANG II in this kidney, injections of ANG II into renal artery were performed 6 wk after clipping of the kidney and compared with normotensive controls. The renal blood flow (RBF) response to 2.5 ng ANG II was measured by a Transonic transit-time flowmeter, before and after indomethacin and candesartan treatment, and analyzed by a computer program. The RBF response to 5 ng arginine-vasopressin (AVP) was examined for comparison with ANG II. The mRNA for AT1Aand AT1Bas well as Western blotting for AT1R in renal resistance vessels were determined, and plasma renin activity (PRA) was measured. Systolic blood pressure was 183 ± 4 mmHg in 2K1C rats compared with 113 ± 1 mmHg in controls ( P < 0.001). PRA was significantly increased in 2K1C animals ( P < 0.05). Injection of ANG II reduced RBF with 10 ± 2% in the nonclipped kidney and 24 ± 3% in controls ( P < 0.001). After indomethacin, the RBF response increased from 10 ± 2 to 20 ± 3% ( P < 0.02) in 2K1C rats and from 24 ± 3 to 34 ± 6% in controls ( P < 0.01). The doses of candesartan needed to completely inhibit RBF response to ANG II were 30 μg/kg in the nonclipped kidney and 100 μg/kg in controls ( P < 0.001). Western blotting and mRNA for AT1Aand AT1Bin the nonclipped kidney were similar to the controls. The results indicate that despite no difference in total AT1R levels, functional AT1R is downregulated in the nonclipped kidney of 2K1C rats.