title: Protection against L-NAME-induced reduction in cardiac output persists even after cessation of angiotensin-converting enzyme inhibitor treatment.
abstract: OBJECTIVE
  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 N(ω) -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.
  
  
  CONCLUSIONS
  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.
authors: Department of Basic Medical Sciences, University of Arizona, College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
authors: L A
authors: LA
authors: Biwer
authors: T L
authors: TL
authors: Broderick
authors: H
authors: H
authors: Xu
authors: C
authors: C
authors: Carroll
authors: T M
authors: TM
authors: Hale
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects* / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004656:Enalapril / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006331:Heart Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006334:Heart Function Tests / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D004656:Enalapril; D019331:NG-Nitroarginine Methyl Ester