Overproduction of NO by an inducible
NO synthase (iNOS) plays a role in the pathophysiology of
septic shock. In such situations, NOS inhibition might be of therapeutic value, although detrimental side effects possibly related to inhibition of constitutive NOS have been reported. The use of L-
canavanine, a selective inhibitor of iNOS, might be more suitable. The aim of the study was to compare in a rodent endotoxic
shock the effects of saline (2 mL/h), N(G)-methyl-
L-arginine(
L-NMMA) (10 mg/kg/h) and L-
canavanine (100 mg/kg/h) on muscle intracellular pH (pHi) and intracellular bioenergetic patterns (
ATP,
phosphocreatine/
inorganic phosphate ratio) using in vivo 31P magnetic resonance spectroscopy (31P MRS). Three groups of anesthetized, mechanically ventilated and paralyzed rats received an
intravenous infusion of 15 mg/kg of
endotoxin. A fourth time-matched control group (n = 8) received 2 mL/h of saline. Mean arterial pressure, femoral blood flow, arterial blood
gases,
lactate,
nitrate level, and 31P nuclear magnetic resonance (31P MRS) measurements were acquired at onset (T = 0), 90 min (T = 90), and 180 min (T180) after the
endotoxin challenge. Femoral
oxygen delivery was calculated as the product of femoral blood flow (mL/min) and arterial
oxygen content.
Endotoxin induced a marked decrease in arterial pressure and femoral
oxygen delivery and an increase in
lactate level. Intracellular pH and
phosphocreatine/
inorganic phosphate ratio decreased.
ATP level did not change. Both
L-NMMA and L-
canavanine reversed the
endotoxin-induced decrease in arterial pressure.
L-NMMA attenuated the decrease in femoral
oxygen delivery and the increase in
lactate level while these were corrected by L-
canavanine. Considering 31P MRS derived bioenergetic indices, the
endotoxin-induced decrease in pHi and Pcr/Pi was attenuated by
L-NMMA and corrected by L-
canavanine. In conclusion, in a rodent model of endotoxinic
shock, the continuous infusion of L-
canavanine, a selective iNOS inhibitor, improved the systemic hemodynamic parameters and the intracellular bio-energetic patterns estimated by in vivo 31P MRS. To the contrary, the continuous infusion of both constitutive and inducible NOS inhibitor
L-NMMA was not followed by the same achievement.