IL‐10 Neither Causes Direct Vasorelaxation Nor Reduces Vasoconstriction in Rat Mesenteric Resistance Arteries

Abstract

Perivascular adipose tissue (PVAT) is the fat that surrounds most of the peripheral blood vessels in the body. PVAT is protective and reduces contraction of blood vessels in health. We discovered that in health, PVAT around the rat small mesenteric resistance vessels (MRPVAT) contained a community of immune cells including T cells, B cells, macrophages, NK cells, neutrophils and mast cells. Interleukin (IL)‐10‐‐an anti‐inflammatory cytokine usually produced by T cells, B cells and macrophages‐‐was identified as one of the highly expressed (mRNA) cytokines in MRPVAT. One report suggests that IL‐10 causes relaxation of mouse mesenteric arteries. Hence, we hypothesized that IL‐10 directly causes vasorelaxation and/or reduces vasoconstriction in healthy rats. Male Sprague Dawley rats (12–14 weeks age) were used. Mesenteric resistance arteries expressed the receptor for IL‐10 (tunica intima and media) as determined by immunohistochemistry. Isolated tissue bath and third order mesenteric resistance arteries (without PVAT and with intact endothelium) were used for isometric contractility studies. Increasing concentrations [0.4–100 ng/mL] of recombinant rat (rr) IL‐10 or vehicle was directly added to half‐maximally constricted (phenylephrine PE or thromboxane A2 agonist U46619) vessels. IL‐10 did not reduce contraction, suggesting it was not a direct vasorelaxant. Further, the ability of rrIL‐10 to cause a rightward or downward shift of a vasoconstrictant‐response curve was tested. The vessels were incubated with rrIL‐10 [100 ng/mL or 10 ng/mL] or vehicle for 1.5 hours in the tissue bath followed by a cumulative PE [10−9–10−5 M] or U46619 [10−10–10−5 M] response curve. The maximal contractions or EC50 values (shown in table ) were not statistically different in rrIL‐10 incubated vessels vs vehicle. Thus, acute exposure of exogenous IL‐10 neither caused direct vasorelaxation nor reduced vasoconstriction. Further studies with neutralizing antibody for IL‐10 to vessels ± PVAT will help determine if IL‐10 produced in the PVAT causes vasorelaxation and/or reduction in local vasoconstriction indirectly, thus contributing to the anti‐contractile nature of PVAT.Support or Funding InformationNIH HL70687 −Log EC50 ± SEM (n=6–10 arteries/3–5 rats/curve) Vehicle rrIL‐10 (100 ng/mL) PE curve 5.7± 0.05 5.6±0.05 U46619 curve 7.6±0.28 7.2±0.59 Vehicle rrIL‐10 (10 ng/mL) PE curve 5.7±0.03 5.6±0.04 U46619 curve 7.1±0.12 7.2±0.13