We investigated the effect of euvolemic surgical preparation, on chemical indices of activity of the nitric oxide (NO) system, in anesthetized, acutely prepared rats. The urinary excretion of NO2+NO3 (U(NOX)V) and cGMP (U(cGMP)V) increased progressively during the experiment. Pretreatment with aminoguanidine or dexamethasone, inhibitors of inducible NO synthase (iNOS), prevented the increase in U(NOX)V and U(cGMP)V but had no impact on mean arterial pressure (BP), renal vascular resistance (RVR) or GFR. Since these variables did not change in the conscious rat, the increased U(NOX)V results from some aspect of the acute surgical preparation. When acutely prepared rats received L-NAME, a non-specific NOS inhibitor, BP and RVR increased but paradoxical increases in U(NOX)V and U(cGMP)V were also seen. Nonselective NOS inhibition (+L-NAME) was fatal in 50% of acutely prepared rats, causing cardiac contracture. The same dose of L-NAME produced no deaths in either conscious chronically catheterized rats or in acutely prepared rats, previously subjected to sterile surgery and acute L-NAME in the conscious state. These data indicate that acute, non-sterile surgery induces expression of iNOS, but that the additional NO generated has no obvious cardiovascular/renal actions. Acute U(NOX)V and U(cGMP)V do not predict total NO production, or 'hemodynamically active' NO. Generalized NO inhibition in rats acutely stressed by surgery/anesthesia can be fatal.
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