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Lookup NU author(s): Dr Nikhil Majmudar, Professor Steve RobsonORCiD, Professor Gary Ford
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Aims. β2-adrenoceptor agonists are generally considered to produce endothelium independent vasodilatation through adenylate cyclase. We determined whether nitric oxide contributes to β2-adrenoceptor vasodilatation in human arterial vasculature. Methods. Forearm blood flow responses to brachial intra-arterial infusions of ritodrine (2.5-50 μg min-1), a selective β2-adrenoceptor agonist, were determined in 24 healthy, normotensive subjects (mean age 22 years, 5F) on two occasions with initial and concomitant administration of L-NMMA (800 μg min-1), an NO synthase inhibitor, or noradrenaline (5-30 ng min-1), a control constrictor not affecting basal NO activity. Responses to the endothelium dependent vasodilator serotonin (n = 6) and an endothelium independent vasodilator GTN (n = 9) were also determined. Results. Maximal dilatation to ritodrine during L-NMMA infusion (310 ± 32%; mean + s.e. mean) was reduced compared to that during noradrenaline infusion (417 ± 41%, P < 0.05), as were summary responses (1023 ± 101 vs 1415 ± 130; P < 0.05). Responses to GTN were unaffected by L-NMMA compared to noradrenaline; max 177 ± 26 vs 169 ± 20%, 95% CI for difference - 33,48; P = 0.68; summary response 361 ± 51 vs 396 ± 37, 95% CI -142,71; P = 0.46. Dilator responses to serotonin were reduced by L-NMMA; max 64 ± 20 vs 163 ± 26%, P < 0.01; summary response 129 ± 36 vs 293 ± 60; P < 0.05) and to a greater extent than ritodrine (58 ± 7 vs 25 ± 14%, P < 0.05). Conclusions. β2-adrenoccptor mediated vasodilatation in the human forearm has an NO mediated component. The underlying mechanism for this effect is unclear, but flow mediated vasodilatation is unlikely to be responsible.
Author(s): Majmudar NG, Anumba D, Robson SC, Ford GA
Publication type: Article
Publication status: Published
Journal: British Journal of Clinical Pharmacology
Year: 1999
Volume: 47
Issue: 2
Pages: 173-177
Print publication date: 01/01/1999
ISSN (print): 0306-5251
ISSN (electronic): 1365-2125
Publisher: Wiley-Blackwell Publishing
URL: http://dx.doi.org/10.1046/j.1365-2125.1999.00880.x
DOI: 10.1046/j.1365-2125.1999.00880.x
PubMed id: 10190652
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