2. Academic Validation
  3. Chronic Elevation of Endothelin-1 Alone May Not Be Sufficient to Impair Endothelium-Dependent Relaxation

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

  • Hypertension. 2019 Dec;74(6):1409-1419. doi: 10.1161/HYPERTENSIONAHA.119.13676.
Zachary I Grunewald 1 2,  Thomas J Jurrissen 1 2,  Makenzie L Woodford 1 2,  Francisco I Ramirez-Perez 2 3,  Lauren K Park 1 2,  Ryan Pettit-Mee 1 2,  Thaysa Ghiarone 1 2,  Scott M Brown 4 5,  Mariana Morales-Quinones 1 2,  James R Ball 1,  Kevin F Staveley-O'Carroll 6,  Annayya R Aroor 5,  Paul J Fadel 7,  Pierre Paradis 8,  Ernesto L Schiffrin 8 9,  Shawn B Bender 1 2 4 5,  Luis A Martinez-Lemus 1 2 10,  Jaume Padilla 1 2
Affiliations

Affiliations

  • 1 From the Department of Nutrition and Exercise Physiology (Z.I.G., T.J.J., M.L.W., L.K.P., R.P.-M., J.R.B., J.P.), University of Missouri, Columbia.
  • 2 Dalton Cardiovascular Research Center (Z.I.G., T.J.J., M.L.W., F.I.R.-P., L.K.P., R.P.-M., T.G., M.M.-Q., S.B.B., L.A.M.-L., J.P.), University of Missouri, Columbia.
  • 3 Department of Biological Engineering (F.I.R.-P.), University of Missouri, Columbia.
  • 4 Department of Biomedical Sciences (S.M.B., S.B.B.), University of Missouri, Columbia.
  • 5 Harry S. Truman Memorial Veterans Hospital (S.M.B., A.R.A., S.B.B.), University of Missouri, Columbia.
  • 6 Department of Surgery (K.F.S.-O.), University of Missouri, Columbia.
  • 7 Department of Kinesiology, University of Texas at Arlington (P.J.F.).
  • 8 Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research (P.P., E.L.S.), McGill University, Montreal, Québec, Canada.
  • 9 Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montreal, Québec, Canada.
  • 10 Department of Medical Pharmacology and Physiology (L.A.M.-L.), University of Missouri, Columbia.
PMID: 31630572 DOI: 10.1161/HYPERTENSIONAHA.119.13676
Abstract

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<0.05), which may contribute to the preservation of EDR in conditions characterized by hyperendothelinemia. Collectively, our findings demonstrate that chronic elevation of ET-1 alone may not be sufficient to impair EDR.

Keywords

NO synthase; aorta; blood pressure; humans; hypertension.

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