Title: Nitric oxide might inhibit cerebral cytochrome oxidase in vivo
Authors: Blockx, Helga
Flameng, Willem
De Visscher, Geofrey # ×
Issue Date: 7-Sep-2006
Conference: AVBS location:Brisbane, Queensland, Australia date:7-11 September 2006
Abstract: In vitro studies have proven NO to be able to inhibit mitochondrial cytochrome oxidase in competition with oxygen1. On the other hand, Bellamy and colleagues (2002)2 found that in brain slices NO concentration did not rise above 4nM, and therefore concluded that under physiologic conditions mitochondrial respiration is not antagonized. Also, in previous in vivo experiments we found that cytochrome oxidase is not inhibited by NO in physiologic conditions or during reoxygenation after a brief anoxic period3. However the question remains whether in pathological conditions inhibiting concentrations are reached in vivo. We therefore cerebrally injected LPS in rats and subjected them to NOS inhibition (1400W and l-NAME) and hypoxia. Cerebral hemodynamics and oxidized cytochrome oxidase were investigated using near infrared spectroscopy (NIRS).
A clear cerebral vascular dilatation was found in LPS rats compared to sham and control ([HbO2] (µmol/l): 106.3 ± 16.6, 89.0 ± 9.8 (p= 0.038) and 86.2 ± 13.5 (p= 0.015); [HbT] (µmol/l): 128.8 ± 16.2, 111.4 ± 8.9 (p= 0.028) and 106.0 ± 15.3 (p= 0.01), respectively), confirming the existence of brain inflammation. By plotting oxidized cytochrome oxidase against mean cerebral oxygen saturation (SmcO2) during hypoxia under three conditions (baseline, 1400W and l-NAME), we can compare the effect of low oxygen availability during augmented and normal concentrations of NO. After fitting the curves with a quadratic-linear model, we found the following: the breakpoint of LPS at baseline is shifted to the left compared to control (30.5 ± 3.0 and 35.1 ± 5.7 (p= 0.038), respectively), but this effect was antagonized by iNOS inhibition (baseline: 30.5 ± 3.0 and after 1400W injection: 34.1 ± 1.7 (p=0.023)). In the quadratic part of the fitting, no differences were found, but in the linear part, we found a shift in slope after l-NAME injection in control, sham and LPS groups. This might indicate an effect of NO at low SmcO2 values even in physiologic conditions, but this has to be examined further.
This study might be the first to demonstrate an effect of NO on cytochrome oxidase in vivo. But further experiments have to be performed to affirm these data.

1. Mander P et al., 2005, J Neurosci Res, 79:208-215
2. Bellamy TC et al., 2002, J Biol Chem, 277:31801-31807
3. De Visscher G et al., 2002, JCBFM, 22:515-519
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Experimental Cardiac Surgery (-)
× corresponding author
# (joint) last author

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