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

Author(s)

Lima, Victor V. ^[1] ; Zemse, Saiprasad M. ^[2] ; Chiao, Chin-Wei ^[3] ; Bomfim, Gisele F. ^[4] ; Tostes, Rita C. ^[5] ; Webb, R. Clinton ^[2] ; Giachini, Fernanda R. ^[1]

Affiliation

^[1] Univ Fed Mato Grosso, Inst Biol Sci & Hlth, BR-78600000 Barra Do Garcas, MT - Brazil

^[2] Georgia Regents Univ, Dept Physiol, Augusta, GA - USA

^[3] Natl Taiwan Univ, Dept Pharmacol, Taipei 10764 - Taiwan

^[4] Univ Fed Mato Grosso, Hlth Sci Inst, Barra Do Garcas, MT - Brazil

^[5] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 145, p. 137-143, JAN 15 2016.
• Web of Science Citations: 14

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 eta g/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 mu M) 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 mu M) 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. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 10/52214-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular and renal injury
• Grantee: Rita de Cassia Aleixo Tostes Passaglia
• Support Opportunities: Regular Research Grants