Interleukin-10 negatively modulates extracellular signal-regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion

Alecsander F. Bressan, Gisele A. Fonseca, Rita C. Tostes, R Clinton Webb, Victor Vitorino Lima, Fernanda Regina Giachini

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10 −/− ) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0.25 μL/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min, 14 days) simultaneously, or not, with Ang II. Aortic rings were mounted in a myograph, and concentration-response curves to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 μm, 40 min). Protein expression of vascular ERK 1/2 was determined by Western blot. Ang II infusion increased the maximal contractile response in both WT and IL-10 −/− mice. Concomitant infusion of IL-10 and Ang II prevented hypercontractility in the vasculature. Exogenous IL-10 infusion prevented ERK 1/2 activation and hypercontractility, induced by Ang II. These findings suggest that IL-10 negatively modulates ERK 1/2 activation and prevents hypercontractility during Ang II-induced hypertension.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalFundamental and Clinical Pharmacology
Volume33
Issue number1
DOIs
StatePublished - Feb 1 2019

Keywords

  • MAP kinase
  • cytokine
  • smooth muscle cell and contraction

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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