title: Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, MT, Brazil.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Lima
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, United States.
authors.forename: Saiprasad M
authors.initials: SM
authors.lastname: Zemse
authors.affiliation: Department of Pharmacology, National Taiwan University, Taipei, Taiwan.
authors.forename: Chin-Wei
authors.initials: CW
authors.lastname: Chiao
authors.affiliation: Health Sciences Institute, Federal University of Mato Grosso, Barra do Garças, MT, Brazil.
authors.forename: Gisele F
authors.initials: GF
authors.lastname: Bomfim
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, United States.
authors.forename: R
authors.initials: R
authors.lastname: Clinton Webb
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, MT, Brazil. Electronic address: fernandagiachini@hotmail.com.
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Giachini
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000276:immunology*
chemical_list: D000804:Angiotensin II; D016753:Interleukin-10; D054460:rho-Associated Kinases
keywords: Cytokine; Inflammation; Vascular dysfunction