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Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice

Author:
Lima, Victor V., Zemse, Saiprasad M., Chiao, Chin-Wei, Bomfim, Gisele F., Tostes, Rita C., Clinton Webb, R., Giachini, Fernanda R.
Source:
Life sciences 2016 v.145 pp. 137-143
ISSN:
0024-3205
Subject:
angiotensin II, animal disease models, anti-inflammatory activity, aorta, blood pressure, enzyme inhibition, hypertension, interleukin-10, mice, phenylephrine
Abstract:
Interleukin-10 (IL-10) is a multi-functional cytokine with potent anti-inflammatory properties. We hypothesized that IL-10 limits increased RhoA/Rho-kinase signaling and vascular reactivity in arteries from angiotensin II (Ang II) hypertensive mice.Wild type (WT) and IL-10 knockout (⁻/⁻) mice were infused with Ang II (90ng/min) for 14days. Additionally, WT mice were infused with Ang II and simultaneously infused with exogenous IL-10 (0.5ηg/min, 14days). Aortic rings were mounted in a myograph and concentration-response curve to phenylephrine (PE) were evaluated.After Ang II infusion, blood pressure responses, but not maximal contraction to PE, was greater in IL-10⁻/⁻ mice, compared to WT. Rho-kinase inhibition (Y-27632; 10μM) resulted in a more evident reduction of PE-induced contraction in WT hypertensive mice, when compared to IL-10⁻/⁻ hypertensive mice. IL-10 exogenous infusion prevented the blood pressure increase in Ang II-infused WT mice. The augmented PE-contraction observed in aorta from WT mice infused with Ang II was also prevented by exogenous infusion of IL-10. Additionally, Rho-kinase inhibition (Y-27632; 10μM) abolished the differences in the contractile response to PE between these groups.These results demonstrate that IL-10 counteracts both the pressoric activity of Ang II as well as vascular dysfunction associated with hypertension, partially, modulating the RhoA-Rho kinase pathway. Strategies to enhance IL-10 levels during hypertension may enhance the benefits provided by regular treatments.
Agid:
6062959