Renal effects of nitric oxide in endotoxemia.
Nitric oxide (NO) is postulated to play a key role in the pathophysiology of renal failure in sepsis. Whether the renal effects of increased NO are beneficial or harmful remains unclear. In a porcine model of lipopolysaccharide (LPS)-induced shock, we evaluated the effect of LPS on glomerular filtration rate (GFR) and renal blood flow (RBF). We then administered the nonselective nitric oxide synthase (NOS) inhibitor N(G)-L-arginine methyl ester (L-NAME), and compared its effects on GFR and RBF with those of S-methylisothiourea (SMT), a selective NOS inhibitor, and those of saline. We postulated that SMT, by maintaining constitutive NO, would be more beneficial than either L-NAME or saline. LPS infusion decreased mean arterial pressure (MAP), and increased cardiac output, RBF, and medullary NO content. The increased RBF was diverted to the medulla. There was no evidence of renal dysfunction in the saline-resuscitated group. Both NOS inhibitors increased MAP but decreased RBF, but only L-NAME reduced GFR and increased sodium excretion and renal oxygen extraction. We conclude that NO in endotoxemia is beneficial because it maintains RBF and GFR. Additionally, selective NOS inhibition did not offer any advantages over saline resuscitation.
Cohen
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RI
Division of Pulmonary and Critical Care Medicine, The Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA. rcohen@lij.edu
Hassell
A M
AM
Marzouk
K
K
Marini
C
C
Liu
S F
SF
Scharf
S M
SM
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010101:Oxygen Consumption; D012079:Renal Circulation / Q000187:drug effects; D012151:Resuscitation / Q000379:methods; D012772:Shock, Septic / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013552:Swine
D008070:Lipopolysaccharides; D007550:Isothiuronium; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium; D019331:NG-Nitroarginine Methyl Ester