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Role of nitric oxide and free radicals in the contractile response to non-preactivated leukocytes

Kennedy, S., Work, L., Ferris, P., Miller, A.M., McManus, B., Wadsworth, R.M., and Wainwright, C.L. (1998) Role of nitric oxide and free radicals in the contractile response to non-preactivated leukocytes. European Journal of Pharmacology, 345 (3). pp. 269-277. ISSN 0014-2999 (doi:10.1016/S0014-2999(98)00007-7)

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Publisher's URL: http://dx.doi.org/10.1016/S0014-2999(98)00007-7

Abstract

Previous studies from our laboratory have shown that nitric oxide (NO) can reduce the release of free radicals from activated leukocytes. The aim of this study was to assess the role of endothelium-derived nitric oxide and leukocyte-derived free radicals in the contractile response to non-preactivated leukocytes. Vessel tension studies were performed in rabbit endothelium-intact aortic vessel rings precontracted with 5-hydroxytryptamine (1 μM). Addition of leukocytes isolated from rabbit blood were added to the rings in increasing concentrations (103–106 cell ml−1) under control conditions and in the presence of L-nitroarginine methyl ester (L-NAME 1 mM), D-NAME (1 mM), or superoxide dismutase (100 U ml−1). The responses to superoxide radical (generated by xanthine plus xanthine oxidase, X/XO), hydrogen peroxide, hypochlorite and peroxynitrite were also assessed. The nature of the free radicals released from non-activated isolated leukocytes, zymosan-stimulated leukocytes (in whole blood) and isolated vessel rings was assessed using luminol-enhanced chemiluminescence. Cumulative addition of leukocyte suspensions to aortic rings caused a concentration-dependent contractile response which was abolished by preincubation of the vessel ring withL-NAME. D-NAME and superoxide dismutase were without effect. All the free radicals tested produced a relaxation of the precontracted aortic ring. The response to X/XO was not affected by superoxide dismutase, but abolished by catalase. The responses to hydrogen peroxide and hypochlorite were both found to be dependent upon the presence of endothelium and NO. The response to peroxynitrite was endothelium-independent and was blocked by methylene blue. While the main free radical released from unstimulated leukocytes and vessel rings was superoxide, the main radical released from activated leukocytes was found to be hypochlorite. These results suggest that the vascular contraction seen in response to non-preactivated leukocytes is due to inhibition, by NO, of the release of free radicals from the leukocytes when activated by contact with the vascular endothelium, thus allowing co-released vasoconstrictor substances to exert their effect.

Item Type:Article
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Work, Dr Lorraine and McManus, Ms Barbara and Miller, Dr Ashley and Kennedy, Dr Simon
Authors: Kennedy, S., Work, L., Ferris, P., Miller, A.M., McManus, B., Wadsworth, R.M., and Wainwright, C.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Pharmacology
Journal Abbr.:Eur. J. Pharmacol.
ISSN:0014-2999
ISSN (Online):1879-0712
Published Online:28 April 1998

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