Whether AT1 (angiotenin II type 1) receptor blockade can prevent the decrease in conduit artery FMD (flow-mediated dilatation) during NOS (nitric oxide synthase) inhibition by alternative endothelial pathways has not been explored previously in humans. In 12 healthy subjects, we measured radial artery diameter (echotracking) and flow (Doppler) during FMD induced by sustained reactive hyperaemia during a control period and following NOS inhibition [1.5 mg·min−1·l−1L-NMMA (NG-monomethyl-L-arginine)], after a single oral administration of telmisartan (80 mg) or placebo, using a randomized double-blind cross-over design. In six volunteers, we also assessed the roles of prostacyclin and EDHF (endothelium-derived hyperpolarizing factor) during radial FMD after AT1 receptor blockade by oral administration of aspirin (500 mg) alone, aspirin+L-NMMA or aspirin+L-NMMA+fluconazole (a cytochrome epoxygenases inhibitor; 0.37 mg·min−1·l−1). Telmisartan did not affect radial artery FMD in the control period (10.9±0.6% with placebo compared with 9.9±0.7% with telmisartan), but prevented its decrease after L-NMMA (9.3±0.8% with placebo compared with 12.6±1.2% with telmisartan; P<0.05) with no modification in baseline parameters, hyperaemia and radial artery endothelium-independent dilatation to sodium nitroprusside. Moreover, in telmisartan-treated subjects, radial artery FMD, compared with control (9.0±1.0%), was not modified by aspirin alone (9.4±0.7%) or associated with L-NMMA (9.5±0.5%), but was reduced by the combination of aspirin, L-NMMA and fluconazole (7.5±0.6%; P<0.05). These results demonstrate that AT1 receptor blockade prevents the decrease in conduit artery FMD during NOS inhibition in humans, suggesting the development of a compensatory endothelial mechanism. This mechanism appears to be independent of prostacyclin and could possibly be related to an EDHF release.
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April 2007
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Research Article|
March 01 2007
AT1 receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NOS inhibition in humans
Jeremy Bellien;
Jeremy Bellien
*Department of Pharmacology, Institut National de la Santé et de la Recherche Medicale (INSERM) U644, Institut Federatif de Recherche Multidisciplinaire sur les Peptides (IFRMP) 23, Rouen University Hospital, 76031 Rouen Cedex, France
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Michele Iacob;
Michele Iacob
*Department of Pharmacology, Institut National de la Santé et de la Recherche Medicale (INSERM) U644, Institut Federatif de Recherche Multidisciplinaire sur les Peptides (IFRMP) 23, Rouen University Hospital, 76031 Rouen Cedex, France
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Helene Eltchaninoff;
Helene Eltchaninoff
†Department of Cardiology, INSERM U644, IFRMP 23, Rouen University Hospital, 76031 Rouen Cedex, France
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Ryad Bourkaib;
Ryad Bourkaib
‡GlaxoSmithKline Laboratory, Marly-le-Roi, France
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Christian Thuillez;
Christian Thuillez
*Department of Pharmacology, Institut National de la Santé et de la Recherche Medicale (INSERM) U644, Institut Federatif de Recherche Multidisciplinaire sur les Peptides (IFRMP) 23, Rouen University Hospital, 76031 Rouen Cedex, France
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Robinson Joannides
*Department of Pharmacology, Institut National de la Santé et de la Recherche Medicale (INSERM) U644, Institut Federatif de Recherche Multidisciplinaire sur les Peptides (IFRMP) 23, Rouen University Hospital, 76031 Rouen Cedex, France
Correspondence: Dr Robinson Joannides (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 24 2006
Revision Received:
November 17 2006
Accepted:
November 24 2006
Accepted Manuscript online:
November 24 2006
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2007
Clin Sci (Lond) (2007) 112 (7): 393–401.
Article history
Received:
August 24 2006
Revision Received:
November 17 2006
Accepted:
November 24 2006
Accepted Manuscript online:
November 24 2006
Citation
Jeremy Bellien, Michele Iacob, Helene Eltchaninoff, Ryad Bourkaib, Christian Thuillez, Robinson Joannides; AT1 receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NOS inhibition in humans. Clin Sci (Lond) 1 April 2007; 112 (7): 393–401. doi: https://doi.org/10.1042/CS20060236
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