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

• Published in: Life sciences (1973) Vol. 145; pp. 137 - 143
• Main Authors: Lima, Victor V., Zemse, Saiprasad M., Chiao, Chin-Wei, Bomfim, Gisele F., Tostes, Rita C., Clinton Webb, R., Giachini, Fernanda R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.01.2016
• Subjects: Angiotensin II - administration & dosage; Angiotensin II - immunology; Animals; Aorta - immunology; Aorta - metabolism; Aorta - physiopathology; Blood Pressure; Cytokine; Hypertension - complications; Hypertension - genetics; Hypertension - immunology; Hypertension - physiopathology; Inflammation; Inflammation - complications; Inflammation - genetics; Inflammation - immunology; Inflammation - physiopathology; Interleukin-10 - genetics; Interleukin-10 - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; rho-Associated Kinases - immunology; Signal Transduction; Vascular dysfunction; Inflammation; Cytokine; Vascular dysfunction
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2015.12.009

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.