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 journalArticlepeer-review

9 Scopus citations


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
Issue number1
StatePublished - Jan 1 2016


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

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine


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