AT 1} receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NOS inhibition in humans
Résumé
Whether AT1 receptor blockade can prevent the decrease in conduit artery flow-mediated dilatation during NO-synthase inhibition by endothelial alternative pathways has not previously been explored in humans. In 12 healthy subjects, we measured radial artery diameter (echotracking) and flow (Doppler) during flow-mediated dilatation induced by sustained reactive hyperemia in control period and following NO-synthase inhibition (L-NMMA: 1.5 mg.min -1}.L -1}), after single oral administration of telmisartan (80 mg) or placebo, during a double-blind, randomized, cross-over study. In 6 volunteers, we also assessed the roles of prostacyclin and endothelium-derived hyperpolarizing factor during radial flow-mediated dilatation after AT 1} receptor blockade by oral administration of aspirin (500 mg) alone and associated with L-NMMA and by the addition of the cytochrome epoxygenases inhibitor fluconazole (0.37 mg.min -1}.L -1}). Telmisartan did not affect radial artery flow-mediated dilatation in control period (placebo: 10.9±0.6% vs. telmisartan: 9.9±0.7%) but prevented its decrease after L-NMMA (placebo: 9.3±0.8% vs. telmisartan: 12.6±1.2%, P<0.05) with no modification in baseline parameters, hyperemia and radial artery endothelium-independent dilatation to sodium nitroprusside. Moreover, in telmisartan-treated subjects, the radial flow-mediated dilatation, 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 in fact was reduced by the combination of aspirin, L-NMMA and fluconazole (7.5±0.6%, P<0.05). These results demonstrate that AT 1} receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NO-synthase inhibition in humans suggesting the development of an endothelial compensatory mechanism. This mechanism seems to be independent of prostacyclin and could possibly be related to an endothelium-derived hyperpolarizing factor release.
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