Abstract 21516: Interleukin 10 Deficiency Influences Cyclooxygenase-dependent Endothelial Vasoconstriction
Interleukin 10 (IL10) is the anti-inflamatory, cytokine synthesis inhibitory factor and plays an important role in immune regulation. Mice with homozygous deletion of IL10 gene develop increased inflammatory cytokines and skeletal muscle weakness with increased age, similar to changes observed in older frail humans (Walston J et al, J of Gerontology 2008). Cardiovascular function is an independent predictor of outcomes in aging and role of inflammatory mediators in microvascular/endothelial cell (EC) dysfunction is a known determinant of vascular health. In addition to vasodilation, EC mediates vasoconstriction (especially in aging), either by withdrawal of EC-dependent relaxing/hyperpolarization factors or by production of EC-derived constrictors. EC Cyclooxygenase-1,2-derived, prostanoids involved in contractions, include endoperoxides and prostacyclin, which activate thromboxane-prostanoid receptors of the vascular smooth muscle cells. Hence we tested the hypothesis that IL10 is essential to maintain EC dependent vasorelaxation (vxr) in mice vessels through COX regulation.
Methods/Results: Aortic rings (2mm), isolated from age matched (36 weeks) Wild Type (WT) (n=5) and IL10KO (n=5) mice were mounted on a 4 channel DMT myograph, optimally stretched and prepared in physiologic buffer at 37°C for vasoreactivity. Phenylephrine pre-constricted aortic rings from frail IL10KO showed significant vasoconstriction (18%) to 1μM acetylcholine (Ach) while rings from WT showed vxr (88%). This Ach dependent contraction was absent in indomethacin (30 μM) treated IL10KO (∼109% vxr). The vxr in WT was no different from indomethacin treated WT (70%).
Conclusions: Anti-inflammatory effects of IL10 may play an important role in maintaining vxr, given that its absence enhances COX-dependent vasoconstriction through vasoconstrictor prostanoids. We propose this pathway as a possible novel mechanism to explain age related vascular stiffness.
- © 2010 by American Heart Association, Inc.