Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG II in murine aortic rings

Abstract

ANG II stimulates the production of reactive oxygen species and activates proinflammatory cytokines leading to endothelial dysfunction. We hypothesized that the anti-inflammatory cytokine IL-10 counteracts the impairment in endothelium-dependent ACh relaxation caused by ANG II. Aortic rings of C57BL/6 mice were incubated in DMEM in the presence of vehicle (deionized H(2)O), ANG II (100 nmol/l), recombinant mouse IL-10 (300 ng/ml), or both ANG II and IL-10 for 22 h at 37 degrees C. After incubation, rings were mounted in a wire myograph to assess endothelium-dependent vasorelaxation to cumulative concentrations of ACh. Overnight exposure of aortic rings to ANG II resulted in blunted ACh-induced vasorelaxation compared with that shown in untreated rings (maximal response = 44 +/- 3% vs. 64 +/- 3%, respectively; P<0.05). IL-10 treatment significantly restored this impairment in relaxation (63 +/- 2%). In addition, the NADPH oxidase inhibitor apocynin restored the impairment in relaxation (maximal response = 76 +/- 3%). Western blotting showed increased gp91(phox) expression (a subunit of NADPH oxidase) in response to ANG II. Vessels treated with a combination of ANG II and IL-10 showed decreased expression of gp91(phox). Immunohistochemical analysis showed increased gp91(phox) expression in ANG II-treated vessels compared with those treated with combined ANG II and IL-10. We found that the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation in response to long-term incubation with ANG II via decreasing NADPH oxidase expression.

Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats

“…IL-10 induces a Th2 cytokine predominance, which has been shown to be prevalent in successful pregnancies (24,25,36). IL-10 may also reverse the downregulation of suppressor of cytokine synthesis-3 as well as heme oxygenase-1 evident in PE, as well as restore endothelial function and nitric oxide bioavailability by preventing oxidative stress (40,41). All of these effects would be expected to lead to a decrease in blood pressure, endothelial dysfunction, and proteinuria.…”

Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1β

“…Whereas high concentrations of recombinant IL-10 up to 300 ng/ml are commonly used for in vitro and ex vivo experiments (5,20,28,31,38,59), the in vitro endogenous expression of IL-10 rarely exceeds 1 ng/ml, even when cells are stimulated with high concentrations of LPS (100 -1,000 ng/ml) (24,47). Similarly, endogenous IL-10 concentration is even lower in plasma of humans afflicted with various diseases, such as malaria (15) and human African trypanosomiasis (11), or in healthy males injected with 4 ng/kg LPS (13).…”

Protecting against vascular disease in brain

“…In relation to ANG II, treatment with exogenous IL-10 protects against ANG II-induced endothelial dysfunction (293). Genetic deletion of IL-10 greatly increases vascular sensitivity to ANG II (72).…”