Vasodilatation dépendante de l'endothélium (régulation par le système nerveux autonome)

La branche sympathique du système nerveux autonome régule la pression artérielle et la répartition du débit sanguin dans l'organisme. L'action vasodilatatrice des catécholamines au niveau vasculaire est classiquement attribuée à l'activation des récepteurs b1- et b2- adrénergiques exprimés dans les cellules musculaires lisses. Nous avons étudié dans un modèle de vaisseau de conductance, l'aorte de rat, le rôle du récepteur b3-adrénergique dans la régulation du tonus vasculaire par le système nerveux autonome. Dans ce vaisseau, une approche pharmacologique nous a permis de montrer que les agonistes b3-adrénergiques, SR 58611A et CG P12177, induisent une vasodilatation dépendante de l'endothélium. Cette vasodilatation est inhibée par le blocage du récepteur b3-adrénergique mais pas par celui des récepteurs b1- et b2-adrénergiques. Par biologie moléculaire et immunohistochimie, nous avons confirmé la localisation endothéliale du récepteur b3-adrénergique en montrant son expression spécifiquement endothéliale dans l'aorte de rat...NANTES-BU Sciences (441092104) / SudocSudocFranceF

Preservation of Endothelium-Dependent Relaxation in Atherosclerotic Mice with Endothelium-Restricted Endothelin-1 Overexpression s

ABSTRACT In human atherosclerosis, which is associated with elevated plasma and coronary endothelin (ET)-1 levels, ET A receptor antagonists improve coronary endothelial function. Mice overexpressing ET-1 specifically in the endothelium (eET-1) crossed with atherosclerosis-prone apolipoprotein E knockout mice (Apoe 2/2 ) exhibit exaggerated high-fat diet (HFD)-induced atherosclerosis. Since endothelial dysfunction often precedes atherosclerosis development, we hypothesized that mice overexpressing endothelial ET-1 on a genetic background deficient in apolipoprotein E (eET-1/Apoe 2/2 ) would have severe endothelial dysfunction. To test this hypothesis, we investigated endothelium-dependent relaxation (EDR) to acetylcholine in eET-1/Apoe 2/2 mice. EDR in mesenteric resistance arteries from 8-and 16-week-old mice fed a normal diet or HFD was improved in eET-1/Apoe 2/2 compared with Apoe 2/2 mice. Nitric oxide synthase (NOS) inhibition abolished EDR in Apoe 2/2 . EDR in eET-1/Apoe 2/2 mice was resistant to NOS inhibition irrespective of age or diet. Inhibition of cyclooxygenase, the cytochrome P450 pathway, and endothelium-dependent hyperpolarization (EDH) resulted in little or no inhibition of EDR in eET-1/Apoe 2/2 compared with wild-type (WT) mice. In eET-1/Apoe 2/2 mice, blocking of EDH or soluble guanylate cyclase (sGC), in addition to NOS inhibition, decreased EDR by 36 and 30%, respectively. The activation of 4-aminopyridine-sensitive voltage-dependent potassium channels (K v ) during EDR was increased in eET-1/Apoe 2/2 compared with WT mice. We conclude that increasing eET-1 in mice that develop atherosclerosis results in decreased mutual dependence of endothelial signaling pathways responsible for EDR, and that NOS-independent activation of sGC and increased activation of K v are responsible for enhanced EDR in this model of atherosclerosis associated with elevated endothelial and circulating ET-1

Characterization of beta(3)-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management

ObjectivesThe aim of the present study was to analyze whether beta3-adrenoceptors (β3-ARs) were effectively present and functional in the human internal mammary artery (IMA).BackgroundThe beta1- and beta2-adrenoceptors classically mediate the relaxant effects of catecholamines in the vessels. In vitro and in vivo studies performed in various animal species described vasodilating effects due to activation of a third beta-ARs subtype (β3).MethodsReverse transcription-polymerase chain reaction analysis, Western blot experiments, and pharmacological studies were carried out in human IMA samples harvested from 27 patients undergoing coronary bypass surgery.ResultsThe β3-ARs messenger ribonucleic acid and protein were detected in intact IMA, but were absent in endothelium-free samples. This finding was confirmed by immunohistochemical experiments. In organ baths, a β3-AR agonist, SR 58611A, induced an endothelium-dependent relaxation of phenylephrine-precontracted IMA rings. This vasodilation was not modified by β1/β2-AR antagonists, but was greatly altered in the presence of L-748,337, a selective human β3-AR antagonist. Moreover, the inhibition of nitric oxide (NO) synthases abolished the β3-adrenergic vasodilation, suggesting the involvement of a NO-signaling pathway.ConclusionsThose results demonstrated the presence of β3-ARs in the endothelial layer of human IMA. The present work highlights the role of β3-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension