IL-1β participates in the regulation of vascular hyporeactivity following endotoxemia in rabbit. The mechanism is related to the down-regulation of α1AR expression through activating the JAK2-STAT3 pathway.

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.