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J Physiol Volume 561, Number 2, 575-582, December 1, 2004 DOI: 10.1113/jphysiol.2004.075218
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Nitric oxide is significantly reduced in ex vivo porcine arteries during reverse flow because of increased superoxide production

X Lu1 and G. S Kassab1

1 Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA

Oscillatory and negative flows occur normally in the cardiovascular system, which predispose those regions to atherosclerosis. Nitric oxide (NO) production increases in proportion to the magnitude of flow and is known to be athero-protective. What is not known, however, is the effect of flow reversal on NO concentration ([NO]). The hypothesis of the present study is that [NO] is reduced in reverse flow. An additional hypothesis is that the reduction in [NO] is mediated through an increase in superoxide production during flow reversal. These hypotheses were tested in an ex vivo preparation of porcine elastic and muscular arteries. The flow of a physiological solution through the vessels was regulated in the forward and reverse direction and the effluent was assayed for nitrite levels using a combination of a diazo coupling method and high performance liquid chromatography. Our results show that [NO] is significantly reduced during reverse flow. Furthermore, addition of tempol (superoxide dismutase-mimetic) which is a superoxide scavenger returns the [NO] during reverse flow to mirror those of forward flow. These results have important implications since the action of superoxide is implicated in many cardiovascular diseases, and the present finding suggests that flow reversal should be added to the list.

(Received 5 September 2004; accepted after revision 5 October 2004; first published online 7 October 2004)
Corresponding author G. S. Kassab: Department of Biomedical Engineering, University of California, Irvine, 204 Rockwell Engineering Center, Irvine, CA 92697-2715, USA. Email: gkassab{at}uci.edu




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