Kyle J Diehl1, Brian L Stauffer2, Jared J Greiner1, Christopher A DeSouza3. 1. Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309. 2. Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309 ; Integrative Vascular Biology Laboratory, Department of Medicine, University of Colorado Denver and the Health Sciences Center, Aurora, CO 80045 ; Integrative Vascular Biology Laboratory, Denver Health Medical Center, Denver, CO 80204. 3. Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309 ; Integrative Vascular Biology Laboratory, Department of Medicine, University of Colorado Denver and the Health Sciences Center, Aurora, CO 80045.
Abstract
BACKGROUND: Modest elevations in plasma low-density lipoprotein (LDL)-cholesterol have been shown to confer a significant increase in cardiovascular risk. Endothelin (ET)-1 is a vasoconstrictor peptide with proatherogenic properties. The experimental aim of this study was to determine whether ET-1 system activity is elevated in adults with borderline high LDL-cholesterol, independent of other cardiometabolic abnormalities. METHODS: Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of ET-1, selective ETA receptor blockade (BQ-123), and non-selective ETA/B blockade (BQ-123 + BQ-788) were determined in 40 middle-aged and older adults (45-70 years): 20 with optimal/near optimal LDL-cholesterol (<3.4 mmol/L) and 20 with borderline-high LDL-cholesterol (3.4-4.1 mmol/L). RESULTS: Both groups demonstrated a similar, non-significant (~10%) reduction in FBF to ET-1. BQ-123 and BQ-123+788 elicited a modest, but significant, increase in FBF (~15-20%) in each group. However, there were no group differences in the FBF responses to either selective ETA or non-selective ETA/B receptor antagonism. CONCLUSION: Borderline-high LDL-C is not associated with increased ET-1 mediated vasoconstrictor tone. Disrupted ET-1 system activity may not contribute to the increased cardiovascular risk burden with borderline-high LDL-cholesterol.
BACKGROUND: Modest elevations in plasma low-density lipoprotein (LDL)-cholesterol have been shown to confer a significant increase in cardiovascular risk. Endothelin (ET)-1 is a vasoconstrictor peptide with proatherogenic properties. The experimental aim of this study was to determine whether ET-1 system activity is elevated in adults with borderline high LDL-cholesterol, independent of other cardiometabolic abnormalities. METHODS: Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of ET-1, selective ETA receptor blockade (BQ-123), and non-selective ETA/B blockade (BQ-123 + BQ-788) were determined in 40 middle-aged and older adults (45-70 years): 20 with optimal/near optimal LDL-cholesterol (<3.4 mmol/L) and 20 with borderline-high LDL-cholesterol (3.4-4.1 mmol/L). RESULTS: Both groups demonstrated a similar, non-significant (~10%) reduction in FBF to ET-1. BQ-123 and BQ-123+788 elicited a modest, but significant, increase in FBF (~15-20%) in each group. However, there were no group differences in the FBF responses to either selective ETA or non-selective ETA/B receptor antagonism. CONCLUSION: Borderline-high LDL-C is not associated with increased ET-1 mediated vasoconstrictor tone. Disrupted ET-1 system activity may not contribute to the increased cardiovascular risk burden with borderline-high LDL-cholesterol.
Authors: O F Wagner; G Christ; J Wojta; H Vierhapper; S Parzer; P J Nowotny; B Schneider; W Waldhäusl; B R Binder Journal: J Biol Chem Date: 1992-08-15 Impact factor: 5.157
Authors: Kyle J Diehl; Brian L Stauffer; Jared J Greiner; Brian R Weil; Christopher A DeSouza Journal: Clin Transl Sci Date: 2012-02-23 Impact factor: 4.689
Authors: Brian R Weil; Christian M Westby; Gary P Van Guilder; Jared J Greiner; Brian L Stauffer; Christopher A DeSouza Journal: Am J Physiol Heart Circ Physiol Date: 2011-06-10 Impact factor: 4.733