Internal medicine

Receptor

Organic chemistry

Enzyme

Angiotensin-converting enzyme

Reperfusion injury

Ischemia

Blood pressure

Biology

Endocrinology

Apoptosis

Chemistry

Bradykinin

Lactate dehydrogenase

Nitric oxide synthase

Nitric oxide

Oxygen

Biochemistry

Medicine

Hypoxia (environmental)

Pharmacology

BioFactors

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.

Inhibition of angiotensin‐converting enzyme protects endothelial cell against hypoxia/reoxygenation injury