Objective  To investigate the effect of interleukin-1β (IL-1β) on vascular calcium se

nsitivity in vitro and in rabbit after endotoxic shock

and to evaluate whether the effect is concerned with protein kinase C (PKC) and Rho kinase.     Methods  A total of 35 adult rabbits were divided into 5 groups: normal control

LPS 30minute

LPS 1hour

LPS 2hour

and LPS 4hour groups (n=7). Rabbits were given 1 mg/kg of LPS (O

111

∶B

4

) via ear-border vein to induce endotoxic shock. Then blood serum and superior mesenteric artery (SMA) were collected to measure IL-1β concentration and calcium sensitivity respectively at correspording time points. The vascular calcium sensitivity was measured with an isolated organ perfusion system. Then the correlation of calcium sensitivity of SMAs with IL-1β concentration in blood serum was analyzed. Effects of different concentrations of IL-1β (25

50

100

150 and 200 ng/ml) on vascular calcium sensitivity of SMAs and the relationship to PKC and Rho kinase were also observed with the aid of their agonists

inhibitors and antagonists (200 ng/ml IL-1β+ 10

-7

mol/L PMA

+10

-7

/10

-6

/10

-5

mol/L staurosporine

+10

-5

mol/L Y27632

and +10

-9

mol/L AngⅡ).     Results  Endotoxic shock model was successfully produced in 30 min to 1 h after LPS injection. The IL-1β concentration of blood serum started to increase at 2 h after injection

and it was then elevated very obviously at 4 h after injection (P0.01). As compared to the control group

the calcium sensitivity of SMAs at early period (30 min and 1 h) after LPS injection was increased significantly (P0.01)

however

in 2 h and 4 h after LPS injection

it was decreased obviously (P0.01). The changes of vascular calcium sensitivity was positively correlated with the IL-1β concentration in blood serum (r=-0.675

P0.05). IL-1β  reduced the calcium sensitivity of SMA in vitro

but the effect was reversed by PKC and Rho kinase agonists.     Conclusion  Our experiments reveal that IL-1β could decrease calcium sensitivity of rabbit in vitro

and its effect

is closely related to PKC and Rho kinase. IL-1β may play a very important role in calcium desensitization following endotoxic shock in rabbits.