Role of oxidative stress in angiotensin-II mediated contraction of human conduit arteries in patients with cardiovascular disease

Background: Angiotensin pi is a powerful vasoconstrictor involved in the development of high blood pressure and in the regulation of cardiovascular growth. Recent reports have suggested that in addition to the classical pathways involved in transducing responses to receptor activation, formation of reactive oxygen species by angiotensin pi may also be involved. We investigated the importance of oxidative stress in angiotensin pi induced contraction in human conduit arteries from patients with cardiovascular disease. Methods and results: Isometric contraction studies using human radial arteries entailed probes modulating the redox-dependent reactions to define the oxidative pathways involved in angiotensin pi contraction. In situ oxidative fluorescence was employed to detect immediate superoxide tissue production in radial and internal mammary arteries. Treatment with TEMPOL, human superoxide dismutase, diphenyleneiodonium, oxypurinol, NG-monomethyl L-arginine considerably decreased contractile response to angiotensin pi in radial arteries. Similarly, angiotensin pi-stimulated arterial superoxide production was reduced in the presence of the above inhibitors. On the contrary, used as controls, norepinephrine vasoconstriction was not associated with increase of superoxide and neither ciprofloxacin nor aminophylline altered basal or angiotensin pi induced superoxide generation. Conclusions: Our findings provide evidence for the role of oxidative pathways in contractile response of human conduit arteries to angiotensin pi. Angiotensin pi induced superoxide anion production may be mediated by multiple inter-dependent rate-limiting enzymes in both types of artery. Our studies may have important implication for future therapeutic approaches involving inhibition of angiotensin pi mediated superoxide generation in hypertension and prevention of cardiovascular disease. Condensed abstract: We studied the role of oxidant species in contraction responses to angiotensin pi in human conduit arteries. Treating radial artery segments with the anti-oxidants with a range of inhibitors, affecting the redox dependent pathways, markedly reduced contraction to angiotensin pi. In parallel experiments, oxidative fluorescence was assessed and compared in human radial and internal mammary artery. Angiotensin pi induced superoxide anion production may be mediated by multiple inter-dependent rate-limiting enzymes in both types of artery. (c) 2005 Elsevier Inc. All rights reserved