Chronic Elevation of Endothelin-1 Alone May Not Be Sufficient to Impair Endothelium-Dependent Relaxation

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide considered to be causally implicated in hypertension and the development of cardiovascular disease. Increased ET-1 is commonly associated with reduced NO bioavailability and impaired vascular function; however, whether chronic elevation of ET...

Full description

Saved in:
Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2019-12, Vol.74 (6), p.1409-1419
Main Authors: Grunewald, Zachary I., Jurrissen, Thomas J., Woodford, Makenzie L., Ramirez-Perez, Francisco I., Park, Lauren K., Pettit-Mee, Ryan, Ghiarone, Thaysa, Brown, Scott M., Morales-Quinones, Mariana, Ball, James R., Staveley-O’Carroll, Kevin F., Aroor, Annayya R., Fadel, Paul J., Paradis, Pierre, Schiffrin, Ernesto L., Bender, Shawn B., Martinez-Lemus, Luis A., Padilla, Jaume
Format: Article
Language:English
Subjects:
Animals
Aorta - physiopathology
Blotting, Western - methods
Endothelial Cells - drug effects
Endothelin-1 - pharmacology
Female
In Vitro Techniques
Mass Spectrometry - methods
Mice
Mice, Inbred C57BL
Models, Animal
Nitric Oxide - metabolism
Sensitivity and Specificity
Vasoconstrictor Agents - pharmacology
Vasodilation - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide considered to be causally implicated in hypertension and the development of cardiovascular disease. Increased ET-1 is commonly associated with reduced NO bioavailability and impaired vascular function; however, whether chronic elevation of ET-1 directly impairs endothelium-dependent relaxation (EDR) remains elusive. Herein, we report that (1) prolonged ET-1 exposure (ie, 48 hours) of naive mouse aortas or cultured endothelial cells did not impair EDR or reduce eNOS (endothelial NO synthase) activity, respectively (P>0.05); (2) mice with endothelial cell–specific ET-1 overexpression did not exhibit impaired EDR or reduced eNOS activity (P>0.05); (3) chronic (8 weeks) pharmacological blockade of ET-1 receptors in obese/hyperlipidemic mice did not improve aortic EDR or increase eNOS activity (P>0.05); and (4) vascular and plasma ET-1 did not inversely correlate with EDR in resistance arteries isolated from human subjects with a wide range of ET-1 levels (r=0.0037 and r=−0.1258, respectively). Furthermore, we report that prolonged ET-1 exposure downregulated vascular UCP-1 (uncoupling protein-1; P
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.119.13676