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Author Notes:

Corresponding author: Brandi M. Wynne. Address where work performed: 1120 15th Street, CA3099, Department of Physiology Georgia Regents University Augusta, GA 30912

Subject:

Research Funding:

This work was supported by the American Heart Association, Grant-in-Aid [15GRNT25700451] to RCW and the National Heart, Lung and Blood Institute at the National Institutes of Health [5R01HL071138-08] to RCW.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Pharmacology & Pharmacy
  • HNO
  • Angeli's Salt
  • Nitroglycerin
  • Endothelin-1
  • Vascular dysfunction
  • NO-CENTER-DOT
  • NITRATE TOLERANCE
  • NITRIC-OXIDE
  • RESISTANCE ARTERIES
  • CEREBRAL-ARTERIES
  • OXIDATIVE STRESS
  • ANGIOTENSIN-II
  • INDUCED RELAXATION
  • AQUEOUS-SOLUTION
  • BLOOD-PRESSURE

Angeli's Salt, a nitroxyl anion donor, reverses endothelin-1 mediated vascular dysfunction in murine aorta

Tools:

Journal Title:

European Journal of Pharmacology

Volume:

Volume 814

Publisher:

, Pages 294-301

Type of Work:

Article | Post-print: After Peer Review

Abstract:

B.V. Nitroglycerin (Gtn) is a treatment for cardiovascular patients due to its vasodilatory actions, but induces tolerance when given chronically. A proposed mechanism is the superoxide (O2-)-oxidative stress hypothesis, which suggests that Gtn increases O2- production. Nitric oxide (NO) exists in three different redox states; the protonated, reduced state, nitroxyl anion (HNO) is an emerging candidate in vascular regulation. HNO is resistant to scavenging and of particular interest in conditions where high levels of reactive oxygen species (ROS) exist. We hypothesize that treatment with Gtn will exacerbate endothelin 1 (ET-1) induced vascular dysfunction via an increase in ROS, while treatment with Angeli's Salt (AS), an HNO donor, will not. Aorta from mice were isolated and divided into four groups: vehicle, ET-1 [0.1 μM, 1 μM], ET-1+Gtn [Gtn 1 μM] and ET-1+AS [AS 1 μM]. Concentration response curves (CRCs) to acetylcholine (ACh) and phenylephrine (Phe) were performed. Aorta incubated with ET-1 (for 20–22 h) exhibited a decreased relaxation response to ACh and an increase in Phe-mediated contraction. Aorta incubated with AS exhibited a reversal in ET-1 induced vascular and endothelial dysfunction. ET-1 increased ROS in aortic vascular smooth muscle cells (VSMCs), visualized by dihydroethidium (DHE) staining. AS incubated reduced this ROS generation, yet maintained with Gtn treatment. These data suggest that aorta incubated with the HNO donor, AS, can reverse ET-1 mediated vascular dysfunction, which may be through a decrease or prevention of ROS generation. We propose that HNO may be vasoprotective and that HNO donors studied as a therapeutic option where other organic nitrates are contraindicative.

Copyright information:

© 2017 Elsevier

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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