Salt intake and non-ACE pathways for intrarenal angiotensin II generation in man

• Published in: Journal of the renin-angiotensin-aldosterone system Vol. 2; no. 1; pp. 14 - 18
• Main Authors: Hollenberg, Norman K, Osei, Suzette Y, Lansang, M Cecilia, Price, Deborah A, Fisher, Naomi DL
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-03-2001
• Subjects: Adult; Angiotensin II - biosynthesis; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Benzimidazoles - pharmacology; Captopril - pharmacology; Diet, Sodium-Restricted; Female; Hemodynamics - drug effects; Humans; Kidney - metabolism; Male; Middle Aged; Renal Circulation - drug effects; Tetrazoles - pharmacology; ACE inhibition; angiotensin II; renin; captopril; candesartan; renal plasma flow
• ISSN: 1470-3203; 1752-8976
• DOI: 10.3317/jraas.2001.002

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.