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Physiological role of endothelin-1 in flow-mediated vasodilatation in humans and impact of cardiovascular risk factors

Abstract : OBJECTIVES: The current study addressed the hypothesis that the local decrease in endothelin-1 (ET-1) bioavailability during sustained flow increases contributes to endothelium-dependent, flow-mediated dilatation (FMD) of conduit arteries and is altered in presence of cardiovascular risk factors. METHODS AND RESULTS: In nine young healthy individuals, the decrease in local ET-1 plasma levels and radial artery FMD in response to hand skin heating (from 34 to 44 °C) was not affected by endothelin type A (ETA) receptor blockade, achieved using the brachial infusion of BQ-123 (100 nmol/min per l of forearm), as compared with physiological saline (0.9% NaCl) infusion. In contrast, endothelin type B (ETB) receptor blockade with BQ-788 (10 nmol/min per l) suppressed the decrease in plasma ET-1 during heating and reduced FMD, without altering nitric oxide release. The coinfusion of BQ-123 did not affect the inhibitory effect of ETB receptor blockade on the decrease in ET-1 plasma levels during heating but prevented the reduction in FMD. Basal radial artery parameters, systemic hemodynamics, and endothelium-independent dilatation to glyceryl trinitrate were not modified by ETA and/or ETB blockade. In a general population of 40 participants without treatment or major cardiovascular diseases, including the nine healthy individuals, the reduction in endothelin-1 level during heating was correlated with FMD (r = -0.55, P < 0.001) and decreased with increased age (r = 0.49, P = 0.001), mean arterial blood pressure (r = 0.48, P = 0.002), and total cholesterol level (r = 0.37, P = 0.024). CONCLUSION: The uptake of endothelin-1 by ETB receptors contributes to conduit artery FMD, preventing its vasoconstrictor action mediated by ETA receptors. The alteration of this mechanism by cardiovascular risk factors may contribute to endothelial dysfunction.
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Submitted on : Sunday, September 29, 2019 - 3:38:28 PM
Last modification on : Thursday, March 3, 2022 - 3:41:27 AM



Jeremy Bellien, Michele Iacob, Christelle Monteil, Isabelle Remy-Jouet, Clothilde Roche, et al.. Physiological role of endothelin-1 in flow-mediated vasodilatation in humans and impact of cardiovascular risk factors. Journal of Hypertension, Lippincott, Williams & Wilkins, 2017, 35 (6), pp.1204-1212. ⟨10.1097/HJH.0000000000001307⟩. ⟨hal-02300714⟩



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