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Oxidative stress and cyclooxygenase‐1 and 2 mediate the hyperresponsiveness of the smooth muscle of the femoral artery of streptozotocin‐treated rats
Author(s) -
Shi Yi,
Man Ricky Y.K.,
Vanhoutte Paul M
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a663-d
Subject(s) - phenylephrine , cyclooxygenase , medicine , endocrinology , streptozotocin , vascular smooth muscle , apocynin , oxidative stress , diabetes mellitus , chemistry , nadph oxidase , biochemistry , blood pressure , smooth muscle , enzyme
Experiments were designed to study the impact of diabetes on responses of vascular smooth muscle. Rings without endothelium of femoral arteries taken from control and diabetic [12 weeks after injection of streptozotocin (STZ)] rats were suspended in organ chambers for the recording of isometric tension. Maximal contractions to potassium chloride were reduced in STZ arteries, illustrating a reduced contractility of the smooth muscle. The concentration‐response curves to phenylephrine and U46619 were shifted significantly to the left, suggesting that STZ induced a hypersensitivity to receptor‐mediated activation of the contractile process. Chronic treatment with apocynin (inhibitor of NADPH oxidase) normalized the maximal response to potassium chloride and prevented the shift to the left of the concentration‐response curves to phenylephrine and U46619, indicating that the functional changes in vascular smooth muscle are due to the chronic oxidative stress during STZ‐induced diabetes. In the STZ arteries, the selective and non‐selective cyclooxygenase [COX] inhibitors (valeryl salicylate [COX‐1], NS‐398 [COX‐2] and indomethacin [COX‐1 and COX‐2]) prevented the hypersensitivity of the smooth muscle to phenylephrine and U46619, suggesting that the two isoforms of cyclooxygenase contribute to the functional changes in vascular smooth muscle responsiveness caused by STZ‐induced diabetes. These data suggest that chronic diabetes and the resulting oxidative stress activate the production of cyclooxygenase derived vasoconstrictor prostanoids in vascular smooth muscle of the rat femoral artery.