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Current Therapeutic Strategies to Mitigate the eNOS Dysfunction in Ischaemic Stroke

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Abstract

Impairment of endothelial nitric oxide synthase (eNOS) activity is implicated in the pathogenesis of endothelial dysfunction in many diseases including ischaemic stroke. The modulation of eNOS during and/or following ischaemic injury often represents a futile compensatory mechanism due to a significant decrease in nitric oxide (NO) bioavailability coupled with dramatic increases in the levels of reactive oxygen species that further neutralise NO. However, applications of a number of therapeutic agents alone or in combination have been shown to augment eNOS activity under a variety of pathological conditions by potentiating the expression and/or activity of Akt/eNOS/NO pathway components. The list of these therapeutic agents include NO donors, statins, angiotensin-converting enzyme inhibitors, calcium channel blockers, phosphodiesterase-3 inhibitors, aspirin, dipyridamole and ellagic acid. While most of these compounds exhibit anti-platelet properties and are able to up-regulate eNOS expression in endothelial cells and platelets, others suppress eNOS uncoupling and tetrahydrobiopterin (an eNOS stabiliser) oxidation. As the number of therapeutic molecules that modulate the expression and activity of eNOS increases, further detailed research is required to reveal their mode of action in preventing and/or reversing the endothelial dysfunction.

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  1. Division of Stroke, Clinical Sciences Building, Nottingham City Hospital Campus, The University of Nottingham, Hucknall Road, Nottingham, NG5 1PB, UK

    Kirtiman Srivastava, Philip M. W. Bath & Ulvi Bayraktutan

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  1. Kirtiman Srivastava
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  2. Philip M. W. Bath
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  3. Ulvi Bayraktutan
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Correspondence to Kirtiman Srivastava.

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Srivastava, K., Bath, P.M.W. & Bayraktutan, U. Current Therapeutic Strategies to Mitigate the eNOS Dysfunction in Ischaemic Stroke. Cell Mol Neurobiol 32, 319–336 (2012). https://doi.org/10.1007/s10571-011-9777-z

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  • DOI: https://doi.org/10.1007/s10571-011-9777-z

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