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TNFα augments depolarization (K+) and agonist‐induced contraction in aortic rings and mesenteric arteries of IL‐10 deficient mice
Author(s) -
Zemse Saiprasad Madhukar,
Hilgers Rob H. P.,
Webb R. Clinton
Publication year - 2007
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.21.6.a1160
Subject(s) - myograph , depolarization , contraction (grammar) , phenylephrine , endocrinology , medicine , agonist , chemistry , mesenteric arteries , saline , receptor , artery , blood pressure
Background: TNFα is a pro‐inflammatory cytokine that augments contraction by both G‐protein coupled receptor activation and KCl‐induced depolarization. Role of IL‐10 in vascular contraction is still unknown. We hypothesized that IL‐10 restores the increased agonist‐ and depolarization‐induced contraction stimulated by TNFα in both large conduit vessels (aortic rings; Ao) and small resistance‐sized (second‐order mesenteric; MA) arteries. Methods and Results: C57BL6 and IL‐10 deficient male mice were treated with human recombinant TNFα (5 ng/mice/day) or vehicle (saline) for 14 days. Subsequently, Ao and second‐order MA were mounted in a myograph. Contractile properties were analyzed via depolarization with 120 mmol/L KCl and via constructing concentration‐response curves to phenylephrine (PE; 10−9 to 10−5 mol/L). In wild‐type mice, chronic TNFα infusion did not result in an augmented contractile force in response to KCl and PE in both Ao and MA. However, in IL‐10 deficient mice TNFα resulted in an enhanced KCl‐induced contractile force compared to saline‐treated IL‐10 deficient mice in both Ao (15.2 ± 0.3 mN versus 12.4 ± 0.5 mN, respectively; P < 0.05) and MA (8.9 ± 0.8 mN versus 5.3 ± 0.3 mN, respectively; P < 0.05). In IL‐10 deficient mice, TNFα also showed an augmented contractile response to PE compared to saline‐treated (11 ± 1.1 mN versus 6.9 ± 1.1 mN, respectively) with increased sensitivity (pEC50 = 6.77 ± 0.07 versus 7.09 ± 0.02, respectively). Conclusion: IL‐10 plays a vital role in modulating TNFα‐induced augmented contractions in both large conduit arteries and peripheral arteries.