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Salt intake and non-ACE pathways for intrarenal angiotensin II generation in man
Norman K Hollenberg
Departments of Radiology and Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, djpagecapo@ rics.bwh.harvard.edu
Suzette Y Osei
Departments of Radiology and Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
M Cecilia Lansang
Departments of Radiology and Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
Deborah A Price
Departments of Radiology and Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
Naomi DL Fisher
Departments of Radiology and Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
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/1.73m 2) significantly exceeded the response to captopril (118±12 mL/min/1.73m 2; 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.
Key Words: angiotensin II • candesartan • renal plasma flow • renin • ACE inhibition • captopril
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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1,
14-18 (2001)
DOI: 10.3317/jraas.2001.002
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