Elevated Endothelin-1 Vasoconstrictor Tone in Prehypertensive Adults

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 ET _A 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 μg/100 mL tissue/min) was measured in the absence and presence of selective ET _A 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 butnot 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.