Choline acetyltransferase+ lymphocytes regulate endothelial nitric oxide synthase (MUC2P.939)

Abstract Mammalian blood vessels are innervated by adrenergic neurons that increase blood pressure. The neurotransmitter mechanism is dependent upon norepinephrine that mediates contraction of vascular smooth cells to increase arterial resistance. Vasodilation is mediated by acetylcholine, which lowers blood pressure through a mechanism dependent upon relaxation of vascular smooth muscle cells in response to endothelial release of nitric oxide. Endothelial cells are not innervated by cholinergic neurons, and it was unknown whether acetylcholine release by lymphocytes might modulate blood pressure. Here, we observed lymphocytes expressing choline acetyltransferase (ChAT), the enzyme that catalyzes biosynthesis of acetylcholine, in the blood. Co-culture of ChAThi lymphocytes with endothelial cells significantly increased calcium concentration and phosphorylation of eNOS in endothelial cells (p<0.05 vs. ChATlow lymphocytes). Passive transfer of engineered ChAThi Jurkat T cells resulted in an immediate significant decrease in blood pressure in recipient mice to 83±5 % of baseline, while blood pressure after transfer of ChATlow Jurkat T was 104±4 % of baseline (p=0.02). Pre-treatment with the NO synthesis inhibitor L-NG-monomethyl arginine citrate prevented the blood pressure reduction by ChAThi Jurkat T cells, and blood pressure remained at 98%±5% of baseline in these animals (p=0.21). These findings suggest a novel mechanism of lymphocyte-mediated blood pressure regulation.