Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: Biochemical mechanisms

Toshio Miyata, Charles Van Ypersele De Strihou, Yasuhiko Ueda, Kohji Ichimori, Reiko Inagi, Hiroshi Onogi, Naoyoshi Ishikawa, Masaomi Nangaku, Kiyoshi Kurokawa

Research output: Contribution to journalArticlepeer-review

264 Citations (Scopus)

Abstract

The implication of advanced glycation end products (AGE) in the pathogenesis of atherosclerosis and of diabetic and uremic complications has stimulated a search for AGE inhibitors. This study evaluates the AGE inhibitory potential of several well-tolerated hypotensive drugs. Olmesartan, an angiotensin II type I receptor (AIIR) antagonist, as well as temocaprilat, an angiotensin-converting enzyme (ACE) inhibitor, unlike nifedipine, a calcium blocker, inhibit in vitro the formation of two AGE, pentosidine and Nε-carboxymethyllysine (CML), during incubation of nonuremic diabetic, nondiabetic uremic, or diabetic uremic plasma or of BSA fortified with arabinose. This effect is shared by all tested AIIR antagonists and ACE inhibitors. On an equimolar basis, they are more efficient than aminoguanidine or pyridoxamine. Unlike the latter two compounds, they do not trap reactive carbonyl precursors for AGE, but impact on the production of reactive carbonyl precursors for AGE by chelating transition metals and inhibiting various oxidative steps, including carbon-centered and hydroxyl radicals, at both the pre- and post-Amadori steps. Their effect is paralleled by a lowered production of reactive carbonyl precursors. Finally, they do not bind pyridoxal, unlike aminoguanidine. Altogether, this study demonstrates for the first time that widely used hypotensive agents, AIIR antagonists and ACE inhibitors, significantly attenuate AGE production. This study provides a new framework for the assessment of families of AGE-lowering compounds according to their mechanisms of action.

Original languageEnglish
Pages (from-to)2478-2487
Number of pages10
JournalJournal of the American Society of Nephrology
Volume13
Issue number10
DOIs
Publication statusPublished - 2002 Oct 1

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: Biochemical mechanisms'. Together they form a unique fingerprint.

Cite this