☆ 4.6 Article

Elevated Endothelin-1 Vasoconstrictor Tone in Prehypertensive Adults

CANADIAN JOURNAL OF CARDIOLOGY (2012)

Journal

CANADIAN JOURNAL OF CARDIOLOGY

Volume 28, Issue 3, Pages 347-353

Publisher

ELSEVIER SCIENCE INC

DOI: 10.1016/j.cjca.2011.11.006

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Funding

National Institutes of Health [HL077450, HL076434, MOI RR00051, ULI RR025780]

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Abstract

Background: Prehypertension (blood pressure [BP] 120-139/80-89 mm Hg) is an independent risk factor for hypertension and cardiovascular disease. Currently, it is unknown whether endothelin (ET)-1-mediated vasoconstrictor tone is elevated with BP in the prehypertensive range. The aims of this study were to determine whether ET-1 vasoconstrictor tone is elevated in prehypertensive adults and, if so, whether ET-1-mediated vasoconstriction contributes to endothelial vasodilator dysfunction in this population. Methods: Forearm blood flow responses to selective ETA receptor blockade (BQ-123; 100 nmol/min) were determined in 26 normotensive adults (age 55 +/- 1 years; BP 112 +/- 1/72 +/- 1 mm Hg) and 30 prehypertensive adults (57 +/- 1 years; BP 130 +/- 1/80 +/- 1 mm Hg). In a subset of participants, forearm blood flow responses to nonselective ET-1 receptor blockade (BQ-123 + BQ-788) were determined. Endothelium-dependent vasodilation to acetylcholine (8.0-32.0 mu g/100 mL tissue/min) was measured in the absence and presence of selective ETA receptor blockade. Results: BQ-123 elicited a significantly greater increase in forearm blood flow in prehypertensive (approximately 20%) than in normotensive (approximately 5%) adults. Addition of BQ-788 resulted in a further increase (P < 0.05) in forearm blood flow in prehypertensive but not in normotensive adults. Forearm blood flow responses to acetylcholine were lower (P < 0.05) in prehypertensive (4.6 +/- 0.3 to 12.6 +/- 0.5 mL/100 mL tissue/min) than in normotensive (4.9 +/- 0.3 to 14.7 +/- 0.8 mL/100 mL tissue/min) adults. Co-infusion of BQ-123 did not affect acetylcholine-induced vasodilation in normotensive adults but resulted in an approximately 20% increase (P < 0.05) in prehypertensive adults. Conclusions: ET-1-mediated vasoconstrictor tone is elevated with prehypertension, contributing to impaired endothelium-dependent vasodilation. ET-1 vasoconstriction may underlie the increased risk of hypertension and cardiovascular disease in prehypertensive adults.

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CEBPB/POU2F2 modulates endothelin 1 expression in prehypertensive SHR vascular smooth muscle cells

Tien-Chun Yang, Mei-Hua Lu, Wei-Jie Wang, Jang-Yi Chen

Summary: The pathogenesis of hypertension involves the enhanced expression of EDN1 gene in vascular smooth muscle cells (VSMCs). POU2F2 and CEBPB have been identified as two main molecules that enhance EDN1 expression in VSMCs. The enhancer region of the Edn1 promoter, from -1309 to -1279 bp, plays a crucial role in this process. The regulation of POU2F2 and CEBPB in VSMCs is highly conserved across species, and their increased expression is observed in remodeled human VSMCs. Understanding this novel regulation mechanism can contribute to the development of future hypertension treatments.

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