Mitochondrial injury underlies hyporeactivity of arterial smooth muscle in severe shock

Abstract

Background Our previous data showed membrane hyperpolarization of arteriolar smooth muscle cells (ASMCs) caused by adenosine triphosphate (ATP)-sensitive potassium channels (K ATP) activation contributed to vascular hyporeactivity in shock. Despite supply of oxygen and nutrients, vascular hyporeactivity to vasoconstrictor agents still remains, which may result from low ATP level. The study was designed to investigate shock-induced mitochondrial changes of rat ASMCs in the genesis and treatment of hypotension in severe shock. Methods The animals were divided into four groups: controls, hemorrhagic shock, CsAshock (preadministration of cyclosporin A before bleeding), and ATRCsAshock (preadministration of atractyloside, followed by CsA and bleeding). ASMCs were isolated and the ultrastructure and function of ASMC mitochondria and the vasoresponsiveness to norepinephrine (NE) was measured on microcirculatory preparations. Results Ultrastructurally, the hemorrhagic shock group showed swollen mitochondria with poorly defined cristae. In this group, the number of ASMCs with low mitochondrial membrane potential (Δ m) was increased by 49.7%, and the intracellular ATP level was reduced by 82.1%, which led to activation of K ATP plasma membrane channels with resultant ASMC hyperpolarization and low vasoreactivity. These changes were reduced in the CsAshock group. When mitochondrial damage was aggravated by ATR in the ATRCsAshock group, the CsA did not protect. Compared to the shock group, vasoresponsiveness to NE was much improved in the CsAshock group. Conclusions Mitochondrial ASMC dysfunction is involved in the genesis of reduced vasoreactivity in severe shock. Mitochondrial protection may therefore be a new approach in the treatment of shock-induced hypotension. © 2011 American Journal of Hypertension, Ltd.