Bellien Jérémy, Iacob Michèle, Monteil Christelle, Rémy-Jouet Isabelle, Roche Clothilde, Duflot Thomas, Vendeville Cathy, Gutierrez Laurence, Thuillez Christian, Richard Vincent, Joannidès Robinson
aDepartment of Pharmacology, Rouen University HospitalbInstitut National de la Santé et de la Recherche Médicale (INSERM) U1096cInstitute for Research and Innovation in Biomedicine, Normandy University, University of RouendCentre d'Investigation Clinique (CIC)-INSERM 1404, Rouen University HospitaleEquipe d'Accueil (EA) 4651, Rouen, France.
J Hypertens. 2017 Jun;35(6):1204-1212. doi: 10.1097/HJH.0000000000001307.
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.
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).
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.
本研究探讨了以下假说，即在持续血流增加过程中内皮素 -1（ET-1）生物利用度的局部降低有助于传导动脉的内皮依赖性血流介导的舒张（FMD），并且在存在心血管危险因素时会发生改变。
在9名年轻健康个体中，与输注生理盐水（0.9% NaCl）相比，通过肱动脉输注BQ-123（每升前臂100 nmol/min）实现的A型内皮素（ETA）受体阻断，并未影响因手部皮肤加热（从34°C至44°C）引起的局部ET-1血浆水平降低和桡动脉FMD。相反，用BQ-788（每升10 nmol/min）阻断B型内皮素（ETB）受体可抑制加热期间血浆ET-1的降低并降低FMD，而不改变一氧化氮释放。同时输注BQ-123并不影响ETB受体阻断对加热期间ET-1血浆水平降低的抑制作用，但可防止FMD降低。ETA和/或ETB阻断未改变桡动脉基础参数、全身血流动力学以及对硝酸甘油非内皮依赖性舒张。在包括这9名健康个体在内的40名未接受治疗或无重大心血管疾病的参与者的一般人群中，加热期间内皮素-1水平的降低与FMD相关（r = -0.55，P < 0.001），并且随着年龄增加（r = 0.49，P = 0.001）、平均动脉血压（r = 0.48，P = 0.002）和总胆固醇水平（r = 0.37，P = 0.024）而降低。
ETB受体对内皮素-1的摄取有助于传导动脉FMD，防止其由ETA受体介导的血管收缩作用。心血管危险因素对该机制的改变可能导致内皮功能障碍。
