Angiotensin II (AII) increases vascular superoxide production (Griendling et al. 1994; Berry et al. 2000). We investigated the role of superoxide in the reactivity of human resistance arteries to AII. Resistance arteries were isolated from subcutaneous gluteal biopsies obtained under local anaesthesia (lignocaine 2 %) from healthy volunteers (n = 8, age 70 ± 2 years, mean ± S.E.M.; 31 arteries). The study was approved by the local Hospital Research Ethics Committee and written informed consent obtained from all participants. Arteries were mounted on a Mulvany-Halpern small vessel myograph and pretreated with potassium chloride (124 mM). Arteries were then treated with the antioxidant vitamin C (1 mM, pH buffered), the superoxide dismutase mimetic TEMPOL (1 mM), the xanthine oxidase inhibitor allopurinol (1 mM) or vehicle, for 30 min before a single concentration-response curve to AII (0.1-100 nM) was obtained in each tissue, in the continued presence of vitamin C, TEMPOL or vehicle. Solutions were bubbled with 95% O₂-5% CO₂ throughout all studies. Results (means ± S.E.M.) are shown as % response vs. contraction to potassium chloride. In the presence of vitamin C the potency of AII and the maximum response were reduced (AII vs. vitamin C: pEC₅₀ 8.5 ± 0.2 vs. 8.2 ± 0.1, maximum response 69 ± 15 vs. 34 ± 10% n = 5; ANOVA F = 7.73; P = 0.03). There was little difference in AII responses following treatment with TEMPOL (AII vs. AII + TEMPOL: pEC₅₀ 8.6 ± 0.2 vs. 8.5 ± 0.1; maximum response 87 ± 13 vs. 80 ± 8% n = 7; F = 0.14; P = 0.67). However, pretreatment of tissues with allopurinol caused a major decrease in response to AII (AII vs. AII + allopurinol: pEC₅₀ 8.6 ± 0.1 vs. 8.3 ± 0.1; maximum response 86 ± 11 vs. 22 ± 3% n = 6; F = 35.97; P = < 0.0001). Decreased potency of Ang II after treatment with vitamin C is consistent with involvement of pro-oxidant pathways in the contractile response of human resistance arteries to Ang II. The lack of effect of TEMPOL suggests that superoxide is not the major reactive oxygen species responsible. The results with allopurinol suggest a superoxide-independent role for xanthine oxidase in Ang II-mediated contraction in healthy older subjects.

These studies were supported by British Heart Foundation Programme Grant RG/99001.