title: The role of membrane potential and calcium kinetic changes in the pathogenesis of vascular hyporeactivity during severe shock.
abstract: OBJECTIVE
  To determine the role of membrane potential and intracellular calcium kinetic changes in producing vascular hyporeactivity during severe hemorrhagic shock.
  
  
  METHODS
  Rats were subjected to hemorrhagic shock (HS) for 2 hours. The spinotrapezius muscle was prepared for microscopy and the responses of arterioles in the muscle to norepinephrine (NE) were tested. The resting membrane potentials of isolated arterial strips were measured with a microelectrode. Membrane potential and intracellular Ca2+ ([Ca2+]i) changes in isolated arteriolar 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 resting 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 response increased 15 fold 2 hours after the onset of hemorrhage as compared with normal animals. The state of vasoreactivity was closely related to the resting potential of vascular smooth muscle in hemorrhagic shock, with a correlation coefficient of 0.96. Treatment with glybenclamide, a selective blocker of ATP-sensitive K+ (KATP) channels, decreased the resting potential, increased NE-stimulated [Ca2+]i increase, and partially restored vasoreactivity in severe hemorrhagic shock.
  
  
  CONCLUSIONS
  The results suggested that membrane hyperpolarization and the reduction of NE-stimulated [Ca2+]i increase in smooth muscle cells appeared to contribute to the vascular hyporeactivity in hemorrhagic shock. The mechanism is likely to involve in KATP channels.
authors.affiliation: Department of Pathophysiology, First Military Medical University, Guangzhou 510515, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Jin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*
chemical_list: D015221:Potassium Channels; D005905:Glyburide; D002118:Calcium; D009638:Norepinephrine