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Mechanisms of Disease: roles of nitric oxide and endothelin-1 in delayed cerebral vasospasm produced by aneurysmal subarachnoid hemorrhage

Nature Clinical Practice Cardiovascular Medicine volume 1, pages 110–116 (2004)Cite this article

Abstract

Molecular biologic investigations in the past decades have begun to unravel the intracellular mechanisms involved in vasomotor regulation of cerebral blood vessels and their failure in delayed cerebral vasospasm produced by aneurysmal subarachnoid hemorrhage. Progress in deciphering macrovascular regulatory mechanisms and their failure in delayed cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage have revealed that there are at least two important vasoactive substances—nitric oxide and endothelin-1—that play important roles in the clinical manifestations of subarachnoid-hemorrhage-induced cerebral vasospasm. Nitric oxide is a cell-membrane-permeable free radical gas that accounts for the phenomenon of vasodilatation by a variety of vasodilator agents. Endothelin-1, a 21 amino acid peptide, is one of the most potent constricting factors. Cerebral vasospasm is thought to represent a disturbance in the cerebral vasomotor equilibrium for which these two physiologically antagonistic compounds are at least partly responsible. Advances in our understanding of the molecular responses of the cerebral vasculature to subarachnoid hemorrhage should lead to more comprehensive management as knowledge becomes translated into development of effective pharmacologic agents to reverse or prevent cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

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Figure 1: Time course of the pathophysiology of delayed cerebral vasospasm and clinical vasospasm
Figure 2: Antagonistic effect of nitric oxide on smooth-muscle contraction
Figure 3: Endothelin's role in vasoconstriction in response to ischemia

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Notes

  1. Editor's statement

    An article response has been published in connection with this article. Various editorial issues arose during the publication processes that warrant elucidation.

    Dr Agustinus Suhardja accepted an invitation on behalf of himself and Dr Robert Furchgott to submit a review paper for Nature Clinical Practice Cardiovascular Medicine. A license to publish form was signed by Dr Suhardja, which is irrevocable, and was sent at the time of article submission.

    On the day of printing, Dr Suhardja asked journal staff to remove all references to Dr Furchgott from the article since he had waited until the last minute to confirm with Dr Furchgott that he wanted to be a coauthor, and at that point Dr Furchgott declined to be named as such. The removal of Dr Furchgott’s name was arranged.

    After the journal had been printed, on the day of distribution, Dr Suhardja asked for the article to be withdrawn, but it was too late to stop distribution. The reason given for the requested retraction, after questioning, was that Dr Suhardja had incorporated extensive comments from one peer-reviewer without asking permission and without discussing concerns raised by the peer-reviewer (in any way), despite being invited to do so by the referee and having been given contact information. A contribution from the referee was acknowledged in the article, but without permission. Given the knowledge of the referee’s willingness to work with the authors and the fact that no comment about a lack of communication was made by either party, the journal staff assumed that incorporation of the comments into the paper had been discussed.

    To clarify on behalf of the journal, throughout the editorial process the reasons for each stage and the forms related to the publication of articles are clearly explained to authors; additional information is readily accessible on the journal’s website (http://www.nature.com/clinicalpractice). Questions can be raised at any time before proofs are finalized. The signing of all forms is binding, and must be completed before an article is accepted for publication. Any concerns about authorship and permission to cite information in the form of text or display items from any source other than the authors must be satisfactorily resolved before an article is accepted for publication. Like the readers of Nature Clinical Practice Cardiovascular Medicine, the Editorial Office relies on the honesty and integrity of authors and peer-reviewers. In this case, we acted in good faith upon information received from the author (both before and after publication), and have brought the circumstances to your attention in order to assist you with your interpretation of the article’s content. We welcome your comments on the article; please use the online system to submit them (http://mts-ncpcm.nature.com).

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Acknowledgements

The author would like to thank R Pluta and R Furchgott for their comments and suggestions, R Guillemin and A Strashun for their continuing support and E Neiman for secretarial assistance.

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  1. the Department of Radiology SUNY Downstate Medical Center, Brooklyn, NY, USA

    Agustinus Suhardja

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Correspondence to Agustinus Suhardja.

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Suhardja, A. Mechanisms of Disease: roles of nitric oxide and endothelin-1 in delayed cerebral vasospasm produced by aneurysmal subarachnoid hemorrhage. Nat Rev Cardiol 1, 110–116 (2004). https://doi.org/10.1038/ncpcardio0046

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