Role of nitric oxide in sepsis-induced hyporeactivity in isolated rat lungs.
The aim of the present study was to test the hypothesis that pulmonary microvascular reactivity is depressed in sepsis and that inducible nitric oxide synthase (iNOS) contributes to the vascular hyporeactivity. Rats were made septic by cecal ligation and puncture. After 16 h, pulmonary vascular reactivity was evaluated by measurement of perfusion pressures while the vasculature was challenged with angiotensin II and KCl. The results showed that vascular reactivity was significantly depressed in lungs from septic rats in comparison to sham-operated controls. Pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) restored the depressed vasoreactivity while the nitric oxide (NO) synthase substrate L-arginine (1 mM) reversed the contraction-restoring effect of L-NAME. NO production in lungs from septic rats increased about 4-fold in comparison to sham-operated controls. iNOS protein was expressed in lung tissues, mainly the resistance vessels, from septic rats but not from sham-operated controls. Reverse transcription and polymerase chain reaction also showed a strong induction of iNOS mRNA in lung tissues from septic rats. These results suggest that increased iNOS expression and NO production may contribute to depressed pulmonary vascular reactivity in sepsis.
Li
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Septic Shock Research Program, Naval Medical Research Institute, Bethesda, Maryland 20889, USA.
Fan
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McKenna
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester