TNFα augments depolarization (K+) and agonist‐induced contraction in aortic rings and mesenteric arteries of IL‐10 deficient mice

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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.