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Inhibition of angiotensin‐converting enzyme protects endothelial cell against hypoxia/reoxygenation injury
Author(s) -
Fujita Noriko,
Manabe Hiroki,
Yoshida Norimasa,
Matsumoto Naohito,
Ochiai Jun,
Masui Yasuharu,
Uemura Manabu,
Naito Yuji,
Yoshikawa Toshikazu
Publication year - 2000
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520110404
Subject(s) - bradykinin , nitric oxide , nitric oxide synthase , lactate dehydrogenase , apoptosis , hypoxia (environmental) , chemistry , pharmacology , reperfusion injury , angiotensin converting enzyme , endocrinology , medicine , ischemia , receptor , biochemistry , enzyme , biology , oxygen , organic chemistry , blood pressure
Cardiovascular tissue injury in ischemia/reperfusion has been shown to be prevented by angiotensin‐converting enzyme (ACE) inhibitors. However, the mechanism on endothelial cells has not been assessed in detail. Cultured human aortic endothelial cells (HAEC) were exposed to hypoxia with or without reoxygenation. Hypoxia enhanced apoptosis along with the activation of caspase‐3. Reoxygenation increased lactate dehydrogenase release time‐dependently, along with an increase of intracellular oxygen radicals. ACE inhibitor quinaprilat and bradykinin significantly lessened apoptosis and lactate dehydrogenase release with these effects being diminished by a kinin B2 receptor antagonist and a nitric oxide synthase inhibitor. In conclusion, hypoxia activated the suicide pathway leading to apoptosis of HAEC by enhancing caspase‐3 activity, while subsequent reoxygenation induced necrosis by enhancing oxygen radical production. Quinaprilat could ameliorate both apoptosis and necrosis through the upregulation of constitutive endothelial nitric oxide synthase via an increase of bradykinin, with the resulting increase of nitric oxide.