Characterization of endothelium-dependent relaxations in the mesenteric vasculature: a comparative study with potential pathophysiological relevance

Abstract Background Endothelium-dependent relaxations in human adult mesenteric microvessels involve 3 different main mechanisms: cyclooxygenase (COX)-derived prostanoids, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF), which elicits vascular smooth muscle hyperpolarization and relaxation. There are some pathological conditions with an abnormal balance between mesenteric vasoconstriction and vasodilatation inputs leading to endothelial dysfunction and tissue injury. Purpose The purpose was to characterize the mechanisms mediating endothelium-dependent relaxation and differences in children and adult mesenteric microvessels. Methods Microvessels were dissected from omentum obtained from children (3-6 years old) and adults (25-41 years old) and mounted as ring preparations in a small vessel myograph. Results In microvessels precontracted with a thromboxane analogue, the endothelium-dependent relaxations to bradykinin (10 nmol/L to 30 μmol/L) mediated by EDHF, that is, nonsensitive to COX (10 μmol/L indomethacin) and NO synthase blockade (100 μmol/L N -nitro-l-arginine methyl ester), were higher in children than in adults. When EDHF was blunted by a depolarizing precontraction with KCl, the remaining COX- and NO-dependent relaxations were significantly lower in children. Conclusions The EDHF's role in the endothelium-dependent relaxations is higher in children's vasculature. This suggests that endothelial dysfunction in mesenteric microvessels in children is likely more dependent on EDHF-related mechanisms rather than on NO- or COX-derived prostanoids.