Abstract 139: Vascular Endothelin-1 Activity Increases with Age in Hypertensive Patients

Abstract

Background: Vascular endothelin-1 (ET-1) dependent vasoconstriction is elevated in patients with hypertension. The effect of increasing age on ET-1 activity is unknown. This study investigated the hypothesis that age is directly associated with ET-1 activity in hypertensive patients. Methods: Retrospective analysis of data collected in a prospective clinical study that investigated vascular ET-1 activity in patients with essential hypertension (BP>140/90mmHg). Endothelin-1 activity was expressed as forearm blood flow (FBF) responses as measured by strain-gauge plethysmography during the intra-arterial infusion of the selective endothelin type-A receptor antagonist BQ-123 (100 nmol/min) for 60 minutes. Changes in FBF from baseline in response to BQ-123 were assessed by one-way ANOVA for repeated measures. Association analyses were performed with use of the Pearson correlation coefficient. Results: Data from 40 patients were included in the current analyses. The baseline characteristics of the study population are reported in the table. Infusion of BQ-123 induced a significant increase in FBF from baseline (p<0.001). The percent increase in FBF from baseline at 60 minutes of BQ-123 infusion was significantly directly associated with age (r=0.435; p=0.006), but not with blood pressure, parameters of glucose and lipid metabolism, markers of endothelial activation, and adipocytokine levels (p=NS for all). Conclusions: In patients with essential hypertension, ET-1 activity is directly associated with age. Our findings suggest that, in this population, aging may contribute to vascular damage and cardiovascular disease risk through an enhanced activation of the ET-1 system. Further study is needed to elucidate the mechanisms underlying the association between age and vascular ET-1 activity.