Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers effectively and directly potentiate superoxide scavenging by polymorphonuclear leukocytes from patients with type 2 diabetes mellitus.
BACKGROUND
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) have potent antioxidant effects in addition to antihypertensive effects.


METHODS
We investigated the ability of ACEIs and ARBs to enhance the superoxide scavenging ability of polymorphonuclear leukocytes (PMNLs) from type 2 diabetic patients (n = 32) and healthy subjects (n = 32). The scavenging ability (U/10(3) cells) of superoxide was measured by electron spin resonance. We used ascorbic acid as a positive control antioxidant and tested captopril, temocapril (an inactive form of ACEI), and temocaprilate (an active form of ACEI) as ACEIs, as well as RNH-6270 as an ARB.


RESULTS
Captopril, temocaprilate, and RNH-6270 showed dose-dependent enhancement in scavenging ability. The scavenging ability with captopril and temocaprilate was greater than with RNH-6270. The changes in scavenging ability induced by all of the drugs in diabetic patients were similar to the changes in healthy subjects. A high-glucose medium (400-800 mg/dL) greatly attenuated the drug-induced enhancement of scavenging ability.


CONCLUSIONS
We demonstrated that both ACEIs and ARBs enhance superoxide scavenging by PMNLs from type 2 diabetic patients and that a high-glucose environment markedly attenuates the ability of these drugs to augment superoxide scavenging.
Inukai
Toshihiko
T
Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan. t-inukai@dokkyomed.ac.jp
Yoshida
Noboru
N
Wakabayashi
Sadao
S
Inukai
Yoshihisa
Y
Matsutomo
Rika
R
Takanashi
Keishi
K
Nakamachi
Takashi
T
Takebayashi
Kohzo
K
Aso
Yoshimasa
Y
Takahashi
Kiyoko
K
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001786:Blood Glucose; D002216:Captopril / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D001786:Blood Glucose; D016166:Free Radical Scavengers; D007093:Imidazoles; D013777:Tetrazoles; D013841:Thiazepines; D013481:Superoxides; C069156:temocaprilat; C055603:temocapril hydrochloride; C437965:olmesartan; D002216:Captopril; D013482:Superoxide Dismutase; D001205:Ascorbic Acid