title: Effects of interleukin-1β on vascular reactivity after lipopolysaccharide-induced endotoxic shock in rabbits and its relationship with PKC and Rho kinase.
abstract: Calcium desensitization plays a critical role in the occurrence of vascular hyporeactivity after shock. Interleukin (IL)-1β participates in the regulation of vascular reactivity via both nitric oxide (NO)-dependent and NO-independent mechanisms. However, the specific NO-independent pathway remains to be established. The issue of whether IL-1β modulates vascular reactivity via regulation of calcium sensitivity in the NO-independent mechanism is unclear. In the current study, effects of IL-1β on vascular calcium sensitivity and its relationship with PKC and Rho kinase were investigated in vivo and in vitro using a rabbit model of lipopolysaccharide (LPS)-induced endotoxic shock and superior mesenteric arteries (SMAs), respectively. The calcium sensitivity profile of SMAs displayed a biphasic change after LPS-induced endotoxic shock (significant increase at 0.5 hour and 1 hour after LPS administration and marked decrease after 2 hours) and was negatively related to changes in serum IL-1β. The IL-1 receptor antagonist, IL-1ra (4 μg/mL), partly reversed LPS-induced calcium desensitization. In vitro incubation with IL-1β (50-200 ng/mL) reduced the calcium sensitivity of SMAs and suppressed the activities of Rho kinase and PKC and the phosphorylation of 20-kDa myosin light chain. These effects of IL-1β were shown to be regulated by the PKC agonist, phorbol 12-myristate 13-acetate, and Rho kinase agonist and antagonist, angiotensin II, and Y-27632, respectively. Our results collectively suggest that IL-1β participates in vascular hyporeactivity after endotoxic shock via regulation of vascular calcium sensitivity. Moreover, this regulatory effect of IL-1β seems closely related to downregulation of the activities of PKC and Rho kinase.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing, People's Republic of China.
authors.forename: Jia-lin
authors.initials: JL
authors.lastname: Liang
authors.forename: Guang-ming
authors.initials: GM
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Liang-ming
authors.initials: LM
authors.lastname: Liu
mesh_terms: D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008638:Mesenteric Arteries / Q000187:drug effects; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000577:Amides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011725:Pyridines; D011994:Recombinant Proteins; D000804:Angiotensin II; C108830:Y 27632; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate