Impact of angiotensin-converting enzyme inhibition on renal cortical nitrotyrosine content during increased extracellular glucose concentration.
OBJECTIVE
Experiments evaluated the hypothesis that angiotensin-converting enzyme (ACE) inhibition suppresses hyperglycemia-induced nitrotyrosine (NT) production in the renal cortex.


METHODS
Rats were untreated (UNTR, n = 6) or received the ACE inhibitor enalapril (20 mg/kg/day; ENAL, n = 6) for 2 weeks. Renal cortical slices were incubated for 90 min in media containing 5 (normal) or 20 mmol/L (high) glucose. Superoxide anion (O2*-) and nitrate + nitrite (NO(X)) levels were measured in the media. Superoxide dismutase (SOD) activity and NT content were measured in the tissue homogenate.


RESULTS
In the UNTR group, high glucose increased O2*- and NO(X) production by the renal cortex (P < 0.05 vs. normal glucose). Likewise, NT content and SOD activity of the renal cortex augmented (P < 0.05 vs. normal glucose). In the ENAL group, O2*- production and NT content were glucose-insensitive, but high glucose exerted an exaggerated impact on NO(X) production and SOD activity (P < 0.01 vs. UNTR in high glucose).


CONCLUSIONS
Accelerated NT content in the renal cortex during high-glucose conditions was prevented by ACE inhibitor treatment. It was suggested that, apart from its anti-hypertensive effect, the mechanism of suppressed NT degradation in the renal cortex by the ACE inhibitor enhances both O2*- degradation per se and antioxidative effects including SOD activation.
Ishii
Naohito
N
Department of Clinical Physiology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Ikenaga
Hideki
H
Carmines
Pamela K
PK
Takada
Nobukazu
N
Okazaki
Toshio
T
Nagai
Tatsuo
T
Maeda
Tadakazu
T
Aoki
Yoshikazu
Y
Saruta
Takao
T
Katagiri
Masato
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D009566:Nitrates; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D004656:Enalapril; D013482:Superoxide Dismutase; D005947:Glucose