Stroke/Cerebral Vasospasm

Re^2: Spasmogens and cerebral vasospasm

R Loch Macdonald

On Tue Dec 8, John Zhang wrote
>On Tue Dec 8, Ken McKechnie wrote
>>A very thought provoking paper which highlights some of the shortfalls of invitro studies. Have you considered the possibility of UTP/UDP as a  possible agonist  being released from the clot or surrounding tissue and acting on the P2 receptors?

>Thank you for the comment. I believe Lock Macdonald has some answers to your questions too. (his name was not included in the author's list by mistake, and he submitted this paper). I agree with you that UTP/UDP should be released at least from platelets and act on the P2u receptors in smooth muscle cells from cerebral arteries. In our previous studies, we found P2u receptor in rat basilar smooth muscle and the calcium response is more pronounded to UTP/UDP than that of ATP. In isometric tension, dog basilar contracts two times more to UTP than ATP.

You are correct that there are other sources of ATP and nucleotides possibly.  These include brain cells and inflammatory cells that can infiltrate after the hemorrhage.  I remain skeptical, however, that levels would reach high enough to cause vasospasm.  We have some unpublished measurements of nucleotide levels in human CSF after SAH and these levels are pretty low too.  Some of the activity of hemolysate - at least fresh hemolysate is due to ATP and possibly other nucleotides but the incubated forms - either in vitro (published in JNS - Guan last month) or in vivo (unpublished info I have also to write up yet) suggests that contractile ability persists even as ATP levels decline greatly.  So I think hemoglobin is important.  We need, however, to do better studies in vivo to try to prove what substances are needed.

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