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

Author(s)

Bressan, Alecsander F. ^[1] ; Fonseca, Gisele A. ^[2] ; Tostes, Rita C. ^[3] ; Webb, R. Clinton ^[4] ; Lima, Victor Vitorino ^[1] ; Giachini, Fernanda Regina ^{[1, 2]}

Affiliation

^[1] Univ Fed Mato Grosso, Inst Biol & Hlth Sci, Av Valdon Varjao 6390, BR-78600000 Barra Do Garcas, Mato Grosso - Brazil

^[2] Fed Univ Goias UFG, Inst Biol Sci ICS, Dept Pharmacol, Av Esperanca, Campus Samambaia, BR-74690900 Goiania, Go - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Av Bandeirantes, N3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Augusta Univ, Dept Physiol, 1120 15th St, CA3126, Augusta, GA 30912 - USA

• Document type: Journal article
• Source: FUNDAMENTAL & CLINICAL PHARMACOLOGY; v. 33, n. 1, p. 31-40, FEB 2019.
• Web of Science Citations: 3

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 eta g.min) or vehicle (saline), via osmotic mini-pumps (0.25 mu L/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 eta g/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 mu m, 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. (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