[Nitric oxide/heme oxygenase-1 mediates the antioxidant effect of ACEI in rat aortic rings].

OBJECTIVE

To examine the effect of angiotensin-converting enzyme inhibitor (ACEI) on hydrogen peroxide (H(2)O(2))-induced decrease in contraction of isolated rataortic rings, and to investigate its mechanisms.

METHODS

The thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured.

RESULT: (1) After incubation with captopril (an ACEI with sulfhydryl groups) or perindoprilate (an ACEI without sulfhydryl groups), the decrease in contraction response to PE was prevented in arteries which were pretreated with 300 micromol/L H(2)O(2). (2) Captopril enhanced the HO-1 activity of thoracic aorta. After inhibition of HO-1 activity by ZnPP IX, the protection effect of captopril was abrogated. Hemin (an inducer of HO-1) and bilirubin (a product of HO-1) could mimic the antioxidative effect of captopril. (3) Both L-NAME (an inhibitor of NOS) and methylene blue (an inhibitor of GC) could abolish the protective effect of captopril. (4) SNAP could protect aortic rings against H(2)O(2) attack, and ZnPP IX could cancel the effect of SNAP.

CONCLUSION

Both ACEI with or without sulfhydryl groups could prevent the H(2)O(2) induced decrease in contraction responses to PE in intact aortic rings. The increase of NO and activation of HO-1 might be involved in the mechanism.