Interleukin‐10 released by Natural Regulatory T Cells improves Microvascular Endothelium‐Dependent Relaxation in hypertensive mice

Background Previously, we demonstrated that increased apoptotic CD 4 + CD 25 + ‐regulatory T cells (Tregs) contribute to microvascular impairment in hypertension. Here, we determined the mechanism how Tregs rescue the microvascular endothelial function in hypertension. Methods/Results Hypertension (HT) was induced by infusing angiotensin II (Ang II, 400 ng/kg/day) to sham mice for two weeks. Endothelium‐dependent relaxation (EDR) in response to acetylcholine was significantly reduced in mesenteric resistance artery (MRA) from HT compared to normotensive mice (Sham) (80.1±2.9 vs. 49.6±2.3%, p<0.05). Interestingly, the incubation of MRA from HT mice with the conditioned media of Tregs, isolated from sham mice, significantly improved the EDR (49.6±2.3 vs. 74.4±4.1%, p<0.05), but no effect was observed on MRA from sham. The improvement of the EDR was reversed when MRA were incubated with IL‐10 antibody or IL‐10 antagonist receptor. In vivo treatment of HT mice with IL‐10 (1000 ng/mouse) for two weeks significantly improved the EDR of MRA compared to untreated mice (46.7±2.1 vs. 60.1±2.4%, p<0.05). This improvement was nitric oxide‐dependent since L‐NAME reverses the effect of IL‐10. Incubation of MRA from HT mice with apocynin, significantly improved the EDR (50.6±1.9 vs. 81.1±4.4%, p<0.05). MRA from sham mice incubated with NADPH substrate significantly reduced the EDR. This effect was reversed when MRA was incubated with NADPH substrate and IL‐10. NADPH activity was significantly higher in MRA from HT compared to MRA from sham and from HT incubated with the conditioned media of Tregs. Conclusion Our novel data provide evidence that IL‐10 released by Tregs controls the endothelial function of resistance arteries in hypertension through the inhibition of NADPH activity. These results identify new target for the modulation of microvascular impairment in hypertension.