Premium
Short‐Term ACE Inhibition Produces Long‐Term Protection Against NOS Inhibitor‐Induced Cardiac Dysfunction
Author(s) -
Biwer Lauren Alysse,
Xu Haodong,
Carroll Chad,
Broderick Tom,
Hale Taben Mary
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1054.6
Subject(s) - enalapril , medicine , cardiac function curve , myocardial infarction , heart failure , nitric oxide synthase , ace inhibitor , nitric oxide , cardiology , stroke volume , hydroxyproline , cardiac output , blood pressure , pharmacology , angiotensin converting enzyme , ejection fraction
ACE inhibition produces changes that persist following cessation of treatment, resulting in a reduced inflammatory, proliferative and fibrotic response to the nitric oxide synthase inhibitor L‐NAME. The present study examines the impact of this pre‐treatment on L‐NAME‐ induced cardiac dysfunction. Young adult spontaneously hypertensive rats were treated with enalapril (E+L) or tap water (C, C+L) for 2 weeks followed by a 2‐week washout period. At this point, C+L and E+L rats were given L‐NAME for 10 days. Hearts were perfused via the Langendorff working heart method, mean arterial pressure was assessed via radiotelemetry, and collagen by hydroxyproline assay. L‐NAME increased MAP by a similar magnitude in C+L and E+L. In the LV, prior enalapril treatment tended to decrease collagen content. L‐NAME caused statistically significant decreases in flow‐mediated functional parameters in C+L rats such as cardiac output (Con: 45±11.1mL/min, C+L: 36±11.3mL/min, E+L:47±7.4mL/min), stroke volume, and coronary flow. Despite equivalent impact on arterial pressure and incidence of myocardial infarction, prior enalapril treatment resulted in 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.