Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses

Brandi M. Wynne, Hicham Labazi, Rita C. Tostes, R Clinton Webb

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Hypertension is a disorder affecting millions worldwide, and is a leading cause of death and debilitation in the United States. It is widely accepted that during hypertension and other cardiovascular diseases the vasculature exhibits endothelial dysfunction; a deficit in the relaxatory ability of the vessel, attributed to a lack of nitric oxide (NO) bioavailability. Recently, the one electron redox variant of NO, nitroxyl anion (NO -) has emerged as an endothelium-derived relaxing factor (EDRF) and a candidate for endothelium-derived hyperpolarizing factor (EDRF). NO - is thought to exist protonated (HNO) in vivo, which would make this species more resistant to scavenging. However, no studies have investigated the role of this redox species during hypertension, and whether the vasculature loses the ability to relax to HNO. Thus, we hypothesize that aorta from angiotensin II (AngII)-hypertensive mice will exhibit a preserved relaxation response to Angeli's Salt, an HNO donor. Male C57Bl6 mice, aged 12-14 weeks were implanted with mini-osmotic pumps containing AngII (90 ng/min, 14 days plus high salt chow) or sham surgery. Aorta were excised, cleaned and used to perform functional studies in a myograph. We found that aorta from AngII-hypertensive mice exhibited a significant endothelial dysfunction as demonstrated by a decrease in acetylcholine (ACh)-mediated relaxation. However, vessels from hypertensive mice exhibited a preserved response to Angeli's Salt (AS), the HNO donor. To confirm that relaxation responses to HNO were maintained, concentration response curves (CRCs) to ACh were performed in the presence of scavengers to both NO and HNO (carboxy-PTIO and L-cys, resp.). We found that ACh-mediated relaxation responses were significantly decreased in aorta from sham and almost completely abolished in aorta from AngII-treated mice. Vessels incubated with l-cys exhibited a modest decrease in ACh-mediated relaxations responses. These data demonstrate that aorta from AngII-treated hypertensive mice exhibit a preserved relaxation response to AS, an HNO donor, regardless of a significant endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)41-47
Number of pages7
JournalPharmacological Research
Volume65
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Angiotensin II
Anions
Aorta
Nitric Oxide
Acetylcholine
Hypertension
Oxidation-Reduction
Endothelium-Dependent Relaxing Factors
Biological Availability
Endothelium
nitroxyl
Cause of Death
Cardiovascular Diseases
Salts
Electrons
oxyhyponitrite

Keywords

  • Angiotensin II hypertension
  • Aorta
  • HNO
  • Nitroxyl anion
  • Vascular

ASJC Scopus subject areas

  • Pharmacology

Cite this

Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses. / Wynne, Brandi M.; Labazi, Hicham; Tostes, Rita C.; Webb, R Clinton.

In: Pharmacological Research, Vol. 65, No. 1, 01.01.2012, p. 41-47.

Research output: Contribution to journalArticle

@article{31fca99356f84c77afc1bab262dd22f9,
title = "Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses",
abstract = "Hypertension is a disorder affecting millions worldwide, and is a leading cause of death and debilitation in the United States. It is widely accepted that during hypertension and other cardiovascular diseases the vasculature exhibits endothelial dysfunction; a deficit in the relaxatory ability of the vessel, attributed to a lack of nitric oxide (NO) bioavailability. Recently, the one electron redox variant of NO, nitroxyl anion (NO -) has emerged as an endothelium-derived relaxing factor (EDRF) and a candidate for endothelium-derived hyperpolarizing factor (EDRF). NO - is thought to exist protonated (HNO) in vivo, which would make this species more resistant to scavenging. However, no studies have investigated the role of this redox species during hypertension, and whether the vasculature loses the ability to relax to HNO. Thus, we hypothesize that aorta from angiotensin II (AngII)-hypertensive mice will exhibit a preserved relaxation response to Angeli's Salt, an HNO donor. Male C57Bl6 mice, aged 12-14 weeks were implanted with mini-osmotic pumps containing AngII (90 ng/min, 14 days plus high salt chow) or sham surgery. Aorta were excised, cleaned and used to perform functional studies in a myograph. We found that aorta from AngII-hypertensive mice exhibited a significant endothelial dysfunction as demonstrated by a decrease in acetylcholine (ACh)-mediated relaxation. However, vessels from hypertensive mice exhibited a preserved response to Angeli's Salt (AS), the HNO donor. To confirm that relaxation responses to HNO were maintained, concentration response curves (CRCs) to ACh were performed in the presence of scavengers to both NO and HNO (carboxy-PTIO and L-cys, resp.). We found that ACh-mediated relaxation responses were significantly decreased in aorta from sham and almost completely abolished in aorta from AngII-treated mice. Vessels incubated with l-cys exhibited a modest decrease in ACh-mediated relaxations responses. These data demonstrate that aorta from AngII-treated hypertensive mice exhibit a preserved relaxation response to AS, an HNO donor, regardless of a significant endothelial dysfunction.",
keywords = "Angiotensin II hypertension, Aorta, HNO, Nitroxyl anion, Vascular",
author = "Wynne, {Brandi M.} and Hicham Labazi and Tostes, {Rita C.} and Webb, {R Clinton}",
year = "2012",
month = "1",
day = "1",
doi = "10.1016/j.phrs.2011.07.002",
language = "English (US)",
volume = "65",
pages = "41--47",
journal = "Pharmacological Research",
issn = "1043-6618",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses

AU - Wynne, Brandi M.

AU - Labazi, Hicham

AU - Tostes, Rita C.

AU - Webb, R Clinton

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Hypertension is a disorder affecting millions worldwide, and is a leading cause of death and debilitation in the United States. It is widely accepted that during hypertension and other cardiovascular diseases the vasculature exhibits endothelial dysfunction; a deficit in the relaxatory ability of the vessel, attributed to a lack of nitric oxide (NO) bioavailability. Recently, the one electron redox variant of NO, nitroxyl anion (NO -) has emerged as an endothelium-derived relaxing factor (EDRF) and a candidate for endothelium-derived hyperpolarizing factor (EDRF). NO - is thought to exist protonated (HNO) in vivo, which would make this species more resistant to scavenging. However, no studies have investigated the role of this redox species during hypertension, and whether the vasculature loses the ability to relax to HNO. Thus, we hypothesize that aorta from angiotensin II (AngII)-hypertensive mice will exhibit a preserved relaxation response to Angeli's Salt, an HNO donor. Male C57Bl6 mice, aged 12-14 weeks were implanted with mini-osmotic pumps containing AngII (90 ng/min, 14 days plus high salt chow) or sham surgery. Aorta were excised, cleaned and used to perform functional studies in a myograph. We found that aorta from AngII-hypertensive mice exhibited a significant endothelial dysfunction as demonstrated by a decrease in acetylcholine (ACh)-mediated relaxation. However, vessels from hypertensive mice exhibited a preserved response to Angeli's Salt (AS), the HNO donor. To confirm that relaxation responses to HNO were maintained, concentration response curves (CRCs) to ACh were performed in the presence of scavengers to both NO and HNO (carboxy-PTIO and L-cys, resp.). We found that ACh-mediated relaxation responses were significantly decreased in aorta from sham and almost completely abolished in aorta from AngII-treated mice. Vessels incubated with l-cys exhibited a modest decrease in ACh-mediated relaxations responses. These data demonstrate that aorta from AngII-treated hypertensive mice exhibit a preserved relaxation response to AS, an HNO donor, regardless of a significant endothelial dysfunction.

AB - Hypertension is a disorder affecting millions worldwide, and is a leading cause of death and debilitation in the United States. It is widely accepted that during hypertension and other cardiovascular diseases the vasculature exhibits endothelial dysfunction; a deficit in the relaxatory ability of the vessel, attributed to a lack of nitric oxide (NO) bioavailability. Recently, the one electron redox variant of NO, nitroxyl anion (NO -) has emerged as an endothelium-derived relaxing factor (EDRF) and a candidate for endothelium-derived hyperpolarizing factor (EDRF). NO - is thought to exist protonated (HNO) in vivo, which would make this species more resistant to scavenging. However, no studies have investigated the role of this redox species during hypertension, and whether the vasculature loses the ability to relax to HNO. Thus, we hypothesize that aorta from angiotensin II (AngII)-hypertensive mice will exhibit a preserved relaxation response to Angeli's Salt, an HNO donor. Male C57Bl6 mice, aged 12-14 weeks were implanted with mini-osmotic pumps containing AngII (90 ng/min, 14 days plus high salt chow) or sham surgery. Aorta were excised, cleaned and used to perform functional studies in a myograph. We found that aorta from AngII-hypertensive mice exhibited a significant endothelial dysfunction as demonstrated by a decrease in acetylcholine (ACh)-mediated relaxation. However, vessels from hypertensive mice exhibited a preserved response to Angeli's Salt (AS), the HNO donor. To confirm that relaxation responses to HNO were maintained, concentration response curves (CRCs) to ACh were performed in the presence of scavengers to both NO and HNO (carboxy-PTIO and L-cys, resp.). We found that ACh-mediated relaxation responses were significantly decreased in aorta from sham and almost completely abolished in aorta from AngII-treated mice. Vessels incubated with l-cys exhibited a modest decrease in ACh-mediated relaxations responses. These data demonstrate that aorta from AngII-treated hypertensive mice exhibit a preserved relaxation response to AS, an HNO donor, regardless of a significant endothelial dysfunction.

KW - Angiotensin II hypertension

KW - Aorta

KW - HNO

KW - Nitroxyl anion

KW - Vascular

UR - http://www.scopus.com/inward/record.url?scp=84856009513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856009513&partnerID=8YFLogxK

U2 - 10.1016/j.phrs.2011.07.002

DO - 10.1016/j.phrs.2011.07.002

M3 - Article

VL - 65

SP - 41

EP - 47

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

IS - 1

ER -