IL-1beta alters hemodynamics in newborn intestine: role of endothelin.
Studies were carried out to determine the effects of IL-1beta on newborn intestinal hemodynamics. IL-1beta increased the release of ET-1 by primary endothelial cells in a dose-dependent manner; as well, it reduced expression of the endothelin (ET) type B (ET(B)) receptor on endothelial cells and increased expression of the ET type A (ET(A)) receptor on vascular smooth muscle cells. IL-1beta increased endothelial cell endothelial nitric oxide (NO) synthase (eNOS) expression but did not enhance eNOS activity as evidenced by release of NO(x) into conditioned medium in response to acetylcholine or shear stress. The effects of IL-1beta on flow-induced dilation were evaluated in terminal mesenteric arteries in vitro. Pretreatment with IL-1beta (1 ng; 4 h) significantly attenuated vasodilation in response to flow rates of 100 and 200 microl/min. This effect was mediated, in part, by the endothelin ET(A) receptor; thus selective blockade of ET(A) receptors with BQ610 nearly restored flow-induced dilation. In contrast, exogenous ET-1 only shifted the diameter-flow curve downward without altering the percent vasodilation in response to flow. The effects of IL-1beta on ileal oxygenation were then studied using in vivo gut loops. Intramesenteric artery infusion of IL-1beta upstream of the gut loop caused ileal vasoconstriction and reduced the arterial-venous O(2) difference across the gut loop; consequently, it reduced ileal oxygenation by 60%. This effect was significantly attenuated by pretreatment with BQ610. These data support a linkage between the proinflammatory cytokine IL-1beta and vascular dysfunction within the intestinal circulation, mediated, at least in part, by the ET system.
Nowicki
Philip T
PT
Columbus Children's Research Institute, Children's Hospital, 700 Children's Dr., Columbus, OH 43205, USA. nowickip@pediatrics.ohio-state.edu
D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D016232:Endothelins / Q000378:metabolism*; D007375:Interleukin-1 / Q000008:administration & dosage*; D007422:Intestines / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D013552:Swine
D016232:Endothelins; D007375:Interleukin-1; D009569:Nitric Oxide