Objective   To observe the effect of TNF-α on vascular calcium sensitivity in rabbits with endotoxin-induced shock and its relation with Rho-kinase and prot

ein kinase C (PKC).    Methods   Vascular calcium sensitivity of superior mesenteric artery (SMA) from normal and endotoxin-induced shock rabbits was detected according to the contraction initiated by Ca

2+

under depolarizing conditions (120 mmol/L KCl) using the in vitro angiotasis assay technique. TNF-α level was measured by ELISA. Effect of TNF-α on calcium sensitivity of SMA and the relation between Rho-kinase and PKC were observed.    Results   The vascular reactivity of SMA to Ca

2+

was increased with the cumulative doseresponse curve of SMA to Ca

2+

shifted to the left and the E

max

of Ca

2+

increased in rabbits 30 min and 1 h after LPS intravenous injection (P0.05). However

it was then decreased with the cumulative doseresponse curve of SMA to Ca

2+

shifted to the right and the E

max

of Ca

2+

significantly decreased (P0.01). The serum TNF-α level began to increase

reached its peak

and decreased to its normal level in 2

4 and 6 h

respectively

after LPS administration

but was still higher than that in control group (P0.05

P0.01)

which was negatively correlated with vascular calcium sensitivity. The low and high levels of TNF-α incubated with SMA significantly increased and decreased the vascular reactivity of SMA to Ca

2+

respectively (P0.05

P0.01). However

the PKC inhibitor

staurosporine

had no effect on TNF-α (P0.05).    Conclusion   TNF-α  plays an important role in regulation of the calcium sensitivity of vascular smooth muscle in rabbits with endotoxin-induced shock

which may be related to Rho-kinase but not with PKC.