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Variation in genes in the endothelin pathway and endothelium-dependent and endothelium-independent vasodilation in an elderly population
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
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2013 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 208, no 1, 88-94 p.Article in journal (Refereed) Published
Abstract [en]

Aim Indirect evidences by blockade of the endothelin receptors have suggested a role of endothelin in endothelium-dependent vasodilation. This study aimed to investigate whether circulating levels of endotehlin-1 or genetic variations in genes in the endothelin pathway were related to endothelium-dependent vasodilation. Methods In 1016 seventy-year-old participants of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery (EDV) and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). Plasma endothelin-1 levels were measured and 60 SNPs in genes in the endothelin pathway (ECE1, EDN1, EDNRA, EDNRB) were genotyped. Results No significant associations were found between circulating endothelin levels and EDV or FMD. No single genotype was related to EDV or FMD following adjustment for multiple testing, but a genotype score for 3 SNPs (rs11618266 in EDNRB, rs17675063 in EDNRA, rs3026868 in ECE1) was significantly related to EDV (beta coefficient 0.070, 95% CI 0.0250.12, P=0.002) when adjusting for gender, systolic blood pressure, HDL and LDL cholesterol, serum triglycerides, BMI, diabetes, smoking, antihypertensive medication or statins and CRP. This score was also related to nitroprusside-induced vasodilation in the forearm. Conclusion A combination of genotypes in the endothelin pathway was related to both endothelium-dependent and endothelium-independent vasodilation in forearm resistance vessels, but not in the brachial artery in an elderly population, giving evidence for a role of the endothelin system in resistance vessel reactivity independent of major cardiovascular risk factors.

Place, publisher, year, edition, pages
2013. Vol. 208, no 1, 88-94 p.
Keyword [en]
endothelin, endothelium, vasodilation, vasoreactivity
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-200657DOI: 10.1111/apha.12068ISI: 000317678000011OAI: oai:DiVA.org:uu-200657DiVA: diva2:624962
Available from: 2013-06-03 Created: 2013-06-03 Last updated: 2017-12-06Bibliographically approved

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Lind, LarsSyvänen, Ann-ChristineAxelsson, TomasLundmark, PerLarsson, Anders

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