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 language | English (US) |
|---|---|
| Pages (from-to) | 8-18 |
| Number of pages | 11 |
| Journal | Hypertension Research |
| Volume | 39 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2016 |
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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 journal › Article
}
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 -