Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR: Impact of prior transient ACE inhibition

Lauren A. Biwer, Karen M. D'Souza, Ali Abidali, Danni Tu, Ashley L. Siniard, Matthew Deboth, Matthew Huentelman, Taben Hale

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (l-arginine methyl ester, l-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of l-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. l-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during l-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of l-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts.

Original languageEnglish (US)
Pages (from-to)8-18
Number of pages11
JournalHypertension Research
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Peptidyl-Dipeptidase A
Inbred SHR Rats
Nitric Oxide Synthase
Enalapril
Inflammation
Chemokines
Cytokines
Blood Pressure
Macrophages
Chemokine CX3CL1
Chemokine CCL2
Vascular System Injuries
Interleukin-4
Interleukin-10
Interleukin-6
Arterial Pressure
Collagen
Water
Wounds and Injuries

Keywords

  • Angiotensin-converting enzyme inhibitor
  • cardiac remodeling
  • chemokine
  • cytokine
  • macrophage

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR : Impact of prior transient ACE inhibition. / Biwer, Lauren A.; D'Souza, Karen M.; Abidali, Ali; Tu, Danni; Siniard, Ashley L.; Deboth, Matthew; Huentelman, Matthew; Hale, Taben.

In: Hypertension Research, Vol. 39, No. 1, 01.01.2016, p. 8-18.

Research output: Contribution to journalArticle

Biwer, Lauren A. ; D'Souza, Karen M. ; Abidali, Ali ; Tu, Danni ; Siniard, Ashley L. ; Deboth, Matthew ; Huentelman, Matthew ; Hale, Taben. / Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR : Impact of prior transient ACE inhibition. In: Hypertension Research. 2016 ; Vol. 39, No. 1. pp. 8-18.
@article{4bddc69872bc4466a1cb6c293d3bd128,
title = "Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR: Impact of prior transient ACE inhibition",
abstract = "We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (l-arginine methyl ester, l-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of l-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. l-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during l-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of l-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts.",
keywords = "Angiotensin-converting enzyme inhibitor, cardiac remodeling, chemokine, cytokine, macrophage",
author = "Biwer, {Lauren A.} and D'Souza, {Karen M.} and Ali Abidali and Danni Tu and Siniard, {Ashley L.} and Matthew Deboth and Matthew Huentelman and Taben Hale",
year = "2016",
month = "1",
day = "1",
doi = "10.1038/hr.2015.107",
language = "English (US)",
volume = "39",
pages = "8--18",
journal = "Hypertension Research",
issn = "0916-9636",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR

T2 - Impact of prior transient ACE inhibition

AU - Biwer, Lauren A.

AU - D'Souza, Karen M.

AU - Abidali, Ali

AU - Tu, Danni

AU - Siniard, Ashley L.

AU - Deboth, Matthew

AU - Huentelman, Matthew

AU - Hale, Taben

PY - 2016/1/1

Y1 - 2016/1/1

N2 - We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (l-arginine methyl ester, l-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of l-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. l-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during l-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of l-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts.

AB - We have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (l-arginine methyl ester, l-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of l-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. l-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during l-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of l-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts.

KW - Angiotensin-converting enzyme inhibitor

KW - cardiac remodeling

KW - chemokine

KW - cytokine

KW - macrophage

UR - http://www.scopus.com/inward/record.url?scp=84953280451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953280451&partnerID=8YFLogxK

U2 - 10.1038/hr.2015.107

DO - 10.1038/hr.2015.107

M3 - Article

C2 - 26490086

AN - SCOPUS:84953280451

VL - 39

SP - 8

EP - 18

JO - Hypertension Research

JF - Hypertension Research

SN - 0916-9636

IS - 1

ER -