The role of membrane potential and calcium kinetic changes in the pathogenesis of vascular hyporeactivity during severe shock

Objective To determine the role of membrane potential and intracellular cal cium kinetic changes in producing vascular hyporeactivity during severe hem orrhagic shock. Methods Rats were subjected to hemorrhagic shock (HS) for 2 hours. The spin otrapezius muscle was prepared for microscopy and the responses of arteriol es in the muscle to norepinephrine(NE) were tested. The resting membrane po tentials of isolated arterial strips were measured with a microelectrode. M embrane potential and intracellular Ca2+ ([Ca2+]i) changes in isolated arte riolar smooth muscle cells (ASMCs) were determined with fluorescent probes and a confocal microscopy. Results The arteriolar resting membrane potential was decreased from - 36.7 +/- 6.3 mV in control to -29.2 +/- 5.3 mV concurrent with the increase of vasoreactivity to NE at 20 minutes after HS. At 120 minutes post-HS, the re sting potential hyperpolarized to - 51.9 +/- 9.1 mV, and NE stimulated [Ca2 +]i increase was reduced to 50% of the control values during the appearance of arteriolar hyporeactivity, i.e. the NE threshold of the arteriolar resp onse increased 15 fold 2 hours after the onset of hemorrhage as compared wi th normal animals. The state of vasoreactivity was closely related to the r esting potential of vascular smooth muscle in hemorrhagic shock, with a cor relation coefficient of 0.96. Treatment with glybenclamide, a selective blo cker of ATP-sensitive K+ (K-ATP) channels, decreased the resting potential, increased NE-stimulaled [Ca2+]i increase, and partially restored vasoreact ivity in severe hemorrhagic shock. Conclusion The results suggested that membrane hyperpolarization and the re duction of NE-stimulated [Ca2+]i increase in smooth muscle cells appeared t o contribute to the vascular hyporeactivity in hemorrhagic shock. The mecha nism is likely to involve in KATP channels.