Faculty Opinions recommendation of Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ.

We previously found that nitric oxide synthase (NOS) inhibition fully blocked alkalosis-induced relaxation of piglet pulmonary artery and vein rings. In contrast, NOS inhibition alone had no effect on alkalosis-induced pulmonary vasodilation in isolated piglet lungs. This study sought to identify factors contributing to the discordance between isolated and in situ pulmonary vessels. The roles of pressor stimulus (hypoxia vs. the thromboxane mimetic U-46619), perfusate composition (blood vs. physiological salt solution), and flow were assessed. Effects of NOS inhibition on alkalosis-induced dilation were also directly compared in 150–350-μm-diameter cannulated arteries and 150–900-μm-diameter, angiographically visualized, in situ arteries. Finally, effects of NOS inhibition on alkalosis-induced vasodilation were measured in intact piglets. NOS inhibition with N ω-nitro-l-arginine fully abolished alkalosis-induced vasodilation in all cannulated arteries but failed to alter alkalosis-induced vasodilation in intact lungs. The results indicate that investigation of other factors, such as perivascular tissue (e.g., adventitia and parenchyma) and remote signaling pathways, will need to be carried out to reconcile this discordance between isolated and in situ arteries.

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Constitutive expression of inducible nitric oxide synthase in the mouse ileal mucosa

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.272.2.g383 ◽

1997 ◽

Vol 272 (2) ◽

pp. G383-G392 ◽

Cited By ~ 21

Author(s):

R. A. Hoffman ◽

G. Zhang ◽

N. C. Nussler ◽

S. L. Gleixner ◽

H. R. Ford ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Severe Combined Immunodeficiency ◽

Intestinal Flora ◽

Constitutive Expression ◽

Inos Mrna ◽

Ileal Mucosa ◽

Oxide Synthase ◽

Inducible Nitric Oxide

It has been demonstrated previously that the inducible isoform of nitric oxide synthase (iNOS) is present throughout the intestinal tract in various inflammatory disease processes. Here we demonstrate that iNOS mRNA is present in the ileum but not in the jejunum or colon of normal mice. By Western blot analysis, iNOS protein is also detected in normal ileum, but not in the normal jejunum. However, by 3 h postinjection of 0.5 mg/kg lipopolysaccharide (LPS), iNOS mRNA is also detectable in the jejunum and colon. The enzyme message and protein, localized immunohistochemically by in situ hybridization and iNOS expression, is normally restricted to the villus epithelial cells. The iNOS mRNA was also present in the ilea of mice with defined intestinal flora (anaerobes only), germ-free mice, nude mice, and to a lesser extent in mice with severe combined immunodeficiency. These results suggest that the constitutive presence of iNOS in ileal epithelium indicates a role for this enzyme in maintaining intestinal homeostasis.

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