Volume 2, Number 1, March 2001

Salt intake and non-ACE pathways for intrarenal angiotensin II generation in man
Norman K Hollenberg, Suzette Y Osei, M Cecilia Lansang, Deborah A Price, Naomi DL Fisher

Angiotensin-converting enzyme (ACE) plays a crucial role in the generation of angiotensin II (Ang II) via conversion from angiotensin I (Ang I). There has been substantial recent interest in non-ACE pathways of Ang II generation in the heart, large arteries, and the kidney. In the case of the human kidney, studied when in balance on a low-salt diet, the renal haemodynamic response to Ang II antagonists substantially exceeds the renal response to ACE inhibitors (ACE-I), suggesting that about 30–40% of Ang II-generation occurs via non-ACE pathways. In this study, we examined the relative contribution of non-ACE pathways, by comparing the response to candesartan and to captopril at the top of the dose-response in normal humans when in balance on a low-salt, as well as a high-salt, diet. As anticipated on a low-salt diet, the increase in renal plasma flow (RPF) in response to candesartan (165±14 mL/min/1.73m²) significantly exceeded the response to captopril (118±12 mL/min/1.73m²; p<0.01). In subjects studied on a high-salt diet, the response to candesartan (97±20 mL/min/1.73m²) also significantly exceeded the response to captopril on the same diet (30±15 mL/min/1.73m²; p<0.01). This remarkable response to candesartan in subjects on a high-salt diet, when compared with the response to captopril, suggests that non-ACE-dependent Ang II generation was influenced less than the classical renal pathway with an increase in salt intake, so that the percentage of Ang II generated via the non-ACE pathway rose to the 60–70% range.

JRAAS 2001;2:14-18.

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