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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/H1736    most recent 87.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tawfik, H. E. Articles by Kaufman, S. PubMed PubMed Citation Articles by Tawfik, H. E. Articles by Kaufman, S.

Role of oxidative stress in multiparity-induced endothelial dysfunction

Faculty of Medicine and Dentistry, Departments of ¹Physiology and ²Pharmacology, University of Alberta, Edmonton, Alberta, Canada

Submitted 25 January 2008 ; accepted in final form 23 August 2008

Multiparity is associated with increased risk of cardiovascular disease. We tested whether multiparity induces oxidative stress in rat vascular tissue. Coronary arteries and thoracic aorta were isolated from multiparous and age-matched virgin rats. Relaxation to ACh and sodium nitroprusside (SNP) was measured by wire myography. We also tested the effect of the superoxide dismutase mimetic MnTE2PyP (30 µM), the NADPH oxidase inhibitor apocynin (10 µM), and the peroxynitrite scavenger FeTPPs (10 µM) on ACh-mediated relaxation in coronary arteries. Vascular superoxide anion was measured using the luminol derivative L-012 and nitric oxide (NO) generation by the Griess reaction. Multiparity reduced maximal response and sensitivity to ACh in coronary arteries [maximal relaxation (E_max): multiparous 49 ± 3% vs. virgins 95% ± 3%; EC₅₀: multiparous 135 ± 1 nM vs. virgins 60 ± 1 nM], and in aortic rings (E_max: multiparous 38 ± 3% vs. virgins 79 ± 4%; EC₅₀: multiparous 160 ± 2 nM vs. virgins 90 ± 3 nM). Coronary arteries from the two groups relaxed similarly to SNP. Superoxide anions formation was significantly higher in both coronary arteries (2.8-fold increase) and aorta (4.1-fold increase) from multiparous rats compared with virgins. In multiparous rats, incubation with MnTE2PyP, apocynin, and FeTPPs improved maximal relaxation to ACh (MnTE2PyP: 74 ± 5%; vehicle: 41 ± 5%; apocynin: 73 ± 3% vs. vehicle: 41 ± 3%; FeTPPs: 72 ± 3% vs. vehicle: 46 ± 3%) and increased sensitivity (EC₅₀: MnTE2PyP: 61 ± 0.5 nM vs. vehicle: 91 ± 1 nM; apocynin: 45 ± 3 nM vs. vehicle: 91 ± 6 nM; FeTPP: 131 ± 2 nM vs. vehicle: 185 ± 1 nM). Multiparity also reduced total nitrate/nitrite levels (multiparous: 2.5 ± 2 µmol/mg protein vs. virgins: 7 ± 1 µmol/mg protein) and endothelial nitric oxide synthase protein levels (multiparous: 0.53 ± 0.1 protein/actin vs. virgins: 1.0 ± 0.14 protein/actin). These data suggest that multiparity induces endothelial dysfunction through decreased NO bioavailability and increased reactive oxygen species formation.

nitric oxide synthase; sodium nitroprusside; N^G-nitro-L-arginine methyl ester