Role of nitric oxide (NO) in pulmonary dysfunction associated with experimental cirrhosis.
We examined the functional role of nitric oxide (NO) and nitric oxide synthase (NOS) isoforms in the pulmonary dysfunction seen in cirrhosis. Lungs were isolated from control and carbon tetrachloride (CCl(4))-induced cirrhotic rats and perfused at constant flow with a whole blood mixture. Ventilation with hypoxic gas resulted in attenuated hypoxic pulmonary vasoconstriction (HPV) in lungs from cirrhotic animals. Administration of the non-selective NOS inhibitor N-omega-Nitro-L-Arginine (L-NNA) resulted in HPV responses that were not different between groups. However, inhibition of inducible nitric oxide synthase (iNOS) did not restore cirrhotic HPV responses. Lungs from cirrhotic rats demonstrated enhanced endothelial-dependent vasodilation to vasopressin when preconstricted with hypoxia but not when preconstricted with thromboxane mimetic. Western blot analysis failed to demonstrate differences in pulmonary endothelial NOS (eNOS) or iNOS levels between groups. Our data suggest that, while NO may play a role in mediating the reduced pulmonary vasoreactivity observed in cirrhosis, other vasoactive factors are likely also important modulators of the pulmonary dysfunction seen in this disease.
Nelson
R S
RS
Department of Anesthesiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Eichinger
M R
MR
D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat