IMPACT OF SURGERY ON NITRIC-OXIDE IN RATS - EVIDENCE FOR ACTIVATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE

We investigated the effect of euvolemic surgical preparation, on chemi cal indices of activity of the nitric oxide (NO) system, in anesthetiz ed, acutely prepared rats. The urinary excretion of NO2+NO3 (UNOXV) an d cGMP (UcGMPV) increased progressively during the experiment. Pretrea tment with aminoguanidine or dexamethasone, inhibitors of inducible NO synthase (iNOS), prevented the increase in UNOXV and UcGMPV but had n o impact on mean arterial pressure (BP), renal vascular resistance (RV R) or GFR. Since these variables did not change in the conscious rat, the increased UNOXV results from some aspect of the acute surgical pre paration. When acutely prepared rats received L-NAME, a non-specific N OS inhibitor, BP and RVR increased but paradoxical increases in UNOXV and UcGMPV were also seen. Non selective NOS inhibition (+L-NAME) was fatal in 50% of acutely prepared rats, causing cardiac contracture. Th e same dose of L-NAME produced no deaths in either conscious chronical ly catheterized rats or in acutely prepared rats, previously subjected to sterile surgery and acute L-NAME in the conscious state. These dat a indicate that acute, nonsterile surgery induces expression of iNOS, but that the additional NO generated has no obvious cardiovascular/ren al actions. Acute UNOXV and UcGMPV do not predict total NO production, or ''hemodynamically active'' NO. Generalized NO inhibition in rats a cutely stressed by surgery/anesthesia can be fatal.