It is very difficult for doctor to treat patient with persistent hypotension in the late stage of shock. The aim of present study was to elucidate the reason for lower vasoreactivity in severe shock. Irreversible hemorrhagic shock of rat was reproduced and the vasoreactivity of arteriole in spinotrapezius muscle to norepinephrine (NE) was measured. The resting membrane potential of isolated arterial strips was detected with a microelectrode. The effect of NO on the membrane potential and intracellular ［Ca2＋］i level in isolated arteriolar smooth muscle cells (ASMCs) was determined with fluorescent probes under confocal microscope. KATP channel of ASMCs was measured with patch clamp method. It was shown that membrane hyperpolarization appeared in arteroles 2 h post hemorrhage, while the resting potential was increased from (-36.9±6.3) mV of control value to (-51.0±9.1) mV with the NE threshold increased to 15 times more than preshock value. The hyperpolarization of ASMCs was closely related to vascular hyporeactivity (correlation coefficient 0.96, P＜0.01). The hyperpolarization was enhanced by lack of ATP, increase in H＋，and OONO- in ASMCs. Single KATP channel conducatance, mean open time and open probability was increased in ASMCs, and the increased ［Ca2＋］i level of ASMCs stimulated by NE was reduced to 50% of normal value. The vasoreactivity, blood pressure and survival rate could be improved by the treatment of glybenclamide and NaHCO3. The study indicates that hyperpolarization of ASMCs is a major reason for lower vasoreactivity in severe shock, since it inhibits the voltage dependent Ca2＋ channel (POC) with the reduction of NE stimulated ［Ca2＋］i increase. The decrease in ATP and increase in H+, and OONO- in ASMCs involves in the activation of KATP channel, leading to the ASMCs hyperpolarization.