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

Victor V. Lima, Saiprasad M. Zemse, Chin Wei Chiao, Gisele F. Bomfim, Rita C. Tostes, R Clinton Webb, Fernanda R. Giachini

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Aims 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. Main methods Wild type (WT) and IL-10 knockout (-/-) mice were infused with Ang II (90 ng/min) for 14 days. Additionally, WT mice were infused with Ang II and simultaneously infused with exogenous IL-10 (0.5 ηg/min, 14 days). Aortic rings were mounted in a myograph and concentration-response curve to phenylephrine (PE) were evaluated. Key findings 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; 10 μM) 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; 10 μM) abolished the differences in the contractile response to PE between these groups. Significance 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.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalLife sciences
Volume145
DOIs
StatePublished - Jan 15 2016

Keywords

  • Cytokine
  • Inflammation
  • Vascular dysfunction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Lima, V. V., Zemse, S. M., Chiao, C. W., Bomfim, G. F., Tostes, R. C., Webb, R. C., & Giachini, F. R. (2016). Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice. Life sciences, 145, 137-143. https://doi.org/10.1016/j.lfs.2015.12.009