Stroke/Cerebral Vasospasm

Re: Evidence for VIP and NO as dual neurotransmitters in cerebral arteries

R. M. Wadsworth
r.m.wadsworth@strath.ac.uk

On Tue Dec 8, Marilyn J. Cipolla wrote
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>This is an important study that demonstrates the global involvement of NO in cerebral arteries, both intraluminally (endothelial) and now extraluminally (perivascular neuronal). I have always suspected neuronal NO to be important in these arteries and it has been shown nicely in this study. Could you tell me how specific is the neuronal NO inhibitor that you used? Also, basal NO release by cerebral arteries antagonizes the substantial tone in these vessels, as demonstrated by the 30-40% contraction in the presence of L-NNA. However, this is a rather non-specific NO inhibitor. Do you know the contribution of neuronal vs. endothelial NO to basal NO release in cerebral arteries?

Thanks for your comments.
According to published data, L-NAPNA is selective for neuronal NOS by virtue of selective accumulation within neurons. We have not carried out experiments of our own to verify the selectivity of this compound. However, that is not a crucial point for us, since the preparations that we use have all been endothelium denuded.

Your second point is very interesting: clearly it will depend on the physiological conditions. If there is flow through the artery, then endothelium output of NO will be increased. If there is high physiological tone in the nerves originating in the sphenopalatine and otic ganglia, then neuronal NO would be greater. Unfortunately, we do not have good data about either of these parameters for the cerebral circulation, so far as I am aware.

With best wishes,

Roger Wadsworth.

Wed Dec 16