Enhanced iNOS (inducible nitric oxide synthase) activity may contribute to vascular dysfunction in patients with heart failure. In the present study, we aimed to determine whether iNOS activity contributes to the maintenance of vascular tone in patients with symptomatic heart failure with the use of the highly selective iNOS inhibitor 1400W {N-[3-(aminomethyl)benzyl] acetamidine}. Bilateral forearm blood flow was measured using venous occlusion plethysmography in 12 patients with New York Heart Association class II–IV heart failure and eight matched healthy control subjects during intra-brachial infusion of 1400W (0.1–1 μmol/min), L-NMMA (NG-monomethyl-L-arginine; a non-selective NOS inhibitor; 2–8 μmol/min) and noradrenaline (control vasoconstrictor; 60–480 pmol/min). In both patients and controls, intra-brachial infusion of L-NMMA and noradrenaline caused a dose–dependent reduction in infused forearm blood flow (P<0.05 for both): peak reduction of 32±6% and 37±4% during L-NMMA and 52±6% and 49±5% during noradrenaline respectively (P values were not significant when patients were compared with controls). In contrast, 1400W had no effect on blood flow at 1 μmol/min [−3±4% in patients (95% confidence intervals, −11 to 5%) and 3±8% in controls; P value was not significant]. In conclusion, we have demonstrated that intrabrachial selective iNOS inhibition does not influence forearm blood flow in patients with heart failure. We conclude that iNOS activity does not contribute to peripheral vascular tone in patients with symptomatic heart failure.
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Research Article|
September 13 2006
Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with heart failure
Anna R. Dover;
*Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, U.K.
Correspondence: Dr Anna R. Dover (email [email protected]).
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Stanley Chia;
Stanley Chia
*Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, U.K.
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James W. Ferguson;
James W. Ferguson
†Department of Hepatology, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, U.K.
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Nicholas L. Cruden;
Nicholas L. Cruden
*Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, U.K.
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Ian L. Megson;
Ian L. Megson
‡Free Radical Research Facility, UHI Millennium Institute, Inverness IV3 5SQ, U.K.
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Keith A. A. Fox;
Keith A. A. Fox
*Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, U.K.
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David E. Newby
David E. Newby
*Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, U.K.
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Publisher: Portland Press Ltd
Received:
May 04 2006
Revision Received:
June 19 2006
Accepted:
June 28 2006
Accepted Manuscript online:
June 28 2006
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2006
Clin Sci (Lond) (2006) 111 (4): 275–280.
Article history
Received:
May 04 2006
Revision Received:
June 19 2006
Accepted:
June 28 2006
Accepted Manuscript online:
June 28 2006
Citation
Anna R. Dover, Stanley Chia, James W. Ferguson, Nicholas L. Cruden, Ian L. Megson, Keith A. A. Fox, David E. Newby; Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with heart failure. Clin Sci (Lond) 1 October 2006; 111 (4): 275–280. doi: https://doi.org/10.1042/CS20060104
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