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The Trp64Arg β3-adrenergic receptor gene polymorphism is associated with endothelium-dependent vasodilatation

Journal of Human Hypertension volume 29, pages 134–135 (2015)Cite this article

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Adrenergic receptors (ADR) are a class of G protein-coupled receptors linked to adenyl cyclase that mediate the action of catecholamines in different tissues. ADR represents an integral part of sympathetic nervous system where it is known to have a major role in the onset and development of hypertension through the regulation of arterial stiffness by endothelium-derived NO. 1

The different ADR subtypes are classified according to agonist-mediated responses and exhibit different tissue localization (α1, α2, β1, β2 and β3). β3 Adrenergic receptor (ADRB3), encoded by a gene located in 8p12, is known to modulate endothelium-dependent vasodilatation (EDV) through NO production via endothelial NO synthase (eNOS). ADRB3 stimulation through adrenergic pathways activates the eNOS and promotes the NO–cGMP signalling cascade, resulting in vasodilatation. In anaesthetized mice, ADRB3 stimulation with CL316243 (ADRB3-selective agonist) results in a robust and sustained peripheral vasodilatation and reduction in blood pressure, both effects totally prevented by β-nonspecific blockade with bupranolol, but not with nadolol, a β1/β2-AR antagonist. In conscious dogs, BRL37344 (other ADRB3-selective agonist), exerts hypotensive effects, which persists in sinoaortic-denervated animals. Similar hypotensive response and peripheral vasodilatation have been reported in control conscious dogs infused with SR58611A. In humans, ADRB3 transcripts and protein have been detected in extracts of human coronary microarteries. In the same vascular bed, BRL37344 evokes a sustained dilatations in microvessels preconstricted with endothelin-1. The endogenous catecholamine, norepinephrine, evoked a marked endogenous vasodilatation. This effect has been reported to be resistant to β1/β2-AR blockade but fully abrogated by ARDB3 antagonists.2 Very few studies have specifically investigated the vascular effects of ADRB3 stimulation in humans. ADRB3 antagonists were able to neutralize increased eNOS activity promoted by the administration of epinephrine, supporting the role of activation of eNOS by ADRB3 and providing physiological relevance to these receptors.3

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Authors and Affiliations

  1. Department of Diabetes, Endocrinology and Nutrition, Hospital of Girona Dr Josep Trueta, Girona, Spain

    G Xifra, F J Ortega, W Ricart & J-M Fernández-Real

  2. CIBERobn Fisiopatologia de la Obesidad y Nutrición, Hospital Clínico Universitario, Santiago de Compostela, Choupana, Spain

    G Xifra, A Castro, F J Ortega, W Ricart & J-M Fernández-Real

  3. Department of Internal Medicine, Hospital Josep Trueta, Girona, Spain

    A Castro

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  1. G Xifra
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  2. A Castro
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Correspondence to J-M Fernández-Real.

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Xifra, G., Castro, A., Ortega, F. et al. The Trp64Arg β3-adrenergic receptor gene polymorphism is associated with endothelium-dependent vasodilatation. J Hum Hypertens 29, 134–135 (2015). https://doi.org/10.1038/jhh.2014.17

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