Protection against L-NAME-induced reduction in cardiac output persists even after cessation of angiotensin-converting enzyme inhibitor treatment

L. A. Biwer, T. L. Broderick, H. Xu, C. Carroll, Taben Hale

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aim: We have demonstrated that short-term angiotensin-converting enzyme (ACE) inhibition in adult spontaneously hypertensive rats produces cardiac changes that persist following cessation of treatment that result in a reduced inflammatory, proliferative and fibrotic response to the nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (L-NAME). The present study examines whether prior ACE inhibition with enalapril also protects against L-NAME-induced cardiac dysfunction. Methods: Rats were treated with enalapril (Enal + L) or tap water (Con, Con + L) for 2 weeks followed by a 2-week washout period. At this point, Con + L and Enal + L rats were treated with L-NAME for 10 days. Hearts were perfused in the working mode, mean arterial pressure (MAP) was assessed via radiotelemetry, and myocardial injury was evaluated in hematoxylin and eosin-stained sections. Results: L-NAME increased MAP by a similar magnitude in Con + L and Enal + L. L-NAME-induced statistically significant decreases in flow-mediated functional parameters in Con + L rats including cardiac output, stroke volume and coronary flow. This was prevented by prior enalapril treatment. Prior enalapril did not prevent L-NAME-induced myocardial injury, but may have lessened the degree of it. Regardless of treatment, changes in cardiac function did not correlate with myocardial injury. Conclusion: Despite equivalent impact on MAP and incidence of myocardial infarction, prior enalapril treatment resulted in the preservation of cardiac function following L-NAME. Understanding the mechanisms by which transient ACE inhibition protects against reductions in cardiac function in the absence of ongoing treatment may reveal novel targets for heart failure treatment.

Original languageEnglish (US)
Pages (from-to)156-165
Number of pages10
JournalActa Physiologica
Volume207
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

NG-Nitroarginine Methyl Ester
Angiotensin-Converting Enzyme Inhibitors
Cardiac Output
Enalapril
Peptidyl-Dipeptidase A
Arterial Pressure
Therapeutics
Wounds and Injuries
Withholding Treatment
Inbred SHR Rats
Hematoxylin
Eosine Yellowish-(YS)
Nitric Oxide Synthase
Stroke Volume
Heart Failure
Myocardial Infarction
Water
Incidence

Keywords

  • Angiotensin-converting enzyme inhibitor
  • Arterial pressure
  • Cardiac output
  • Cardiac remodelling
  • Hypertension
  • Spontaneously hypertensive rat

ASJC Scopus subject areas

  • Physiology

Cite this

Protection against L-NAME-induced reduction in cardiac output persists even after cessation of angiotensin-converting enzyme inhibitor treatment. / Biwer, L. A.; Broderick, T. L.; Xu, H.; Carroll, C.; Hale, Taben.

In: Acta Physiologica, Vol. 207, No. 1, 01.2013, p. 156-165.

Research output: Contribution to journalArticle

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