Subcellular Injury of ASMEs Involves in the Genesis of Refractory Hypotension in Severe Shock

Abstract

The Refractory Hypotension (RH) leads to severe hypoperfusion which results in vital organ failure and death. It has been shown that one of the main reasons for RH is Arteriolar Smooth Muscle Cell (ASMC) hyperpolarization, which results in the inhibition of L-type calcium channel and Ca2+ influx after vasoconstrictor stimulation, that finally leads to refractory hypotension during severe shock. The activation of KATP channels by depletion of intracellular ATP content causes ASMC hyperpolarization. It is usually recognized that the depletion of ATP content originates from microcirculatory disturbance and refractory hypotension is only a functional problem of ASMC with treatment using vasopressors, and no morphological changes of smooth muscle cell were reported in RH. This review shows that mitochondrial damage is another important reason for depletion of ATP level and that protection of mitochondrial dysfunction can increase the blood pressure and survival rate during severe shock, which indicated that subcellular injury of ASMCs is involved in the genesis of refractory hypotension. Protecting and repairing ASMC subcellular injury is a new approach to treatment of severe shock.