Endothelial dysfunction and infarct-size relate to impaired EDHF response in rat experimental chronic heart failure

Eur J Heart Fail. 2003 Mar;5(2):147-54. doi: 10.1016/s1388-9842(02)00248-9.

Abstract

Background: The rat coronary ligation model of chronic heart failure has been extensively used to investigate its pathophysiology including the role of endothelial dysfunction. Inconsistent results have been obtained concerning the role of endothelial dilative mediators nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF).

Aims: Our aim was to investigate involvement of NO and EDHF in aortic endothelial dysfunction in this model and the influence of individual infarct sizes. Furthermore, we investigated whether it is justified to regard rats that failed to develop large infarct sizes as SHAM controls.

Methods: We performed coronary ligations and SHAM operations and studied acetylcholine (ACh)-induced relaxations and underlying endothelial mediators in isolated aortic rings 12 weeks after infarction. By then, cardiac and hemodynamic parameters were deteriorated in animals with large myocardial infarctions (large-MI, 35+/-3%), but not those with small myocardial infarctions (small-MI, 5+/-2%).

Results: Large-MI showed decreased ACh-induced relaxation compared to SHAM due to decreased contribution of EDHF which was inversely correlated with individual infarct-size. Interestingly, small-MI showed significantly increased ACh-induced relaxation compared to SHAM due to increased NO contribution.

Conclusions: Our results suggest that impaired aortic endothelial dilatory function in large-MI is mainly due to an impaired EDHF response and strongly depends on individual infarct-size. In addition, endothelium-dependent relaxation of small-MI rats differed from SHAM, indicating that both groups may not be pooled to serve as controls. These results emphasize the importance of infarct-size and choice of the control group, and may explain inconsistencies in previous studies.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Area Under Curve
  • Biological Factors / pharmacology
  • Biological Factors / physiology*
  • Blood Pressure / physiology
  • Cardiac Surgical Procedures
  • Chronic Disease
  • Coronary Circulation / physiology
  • Disease Models, Animal
  • Endothelium, Vascular / anatomy & histology
  • Endothelium, Vascular / physiopathology*
  • Heart Failure / pathology
  • Heart Failure / physiopathology*
  • Heart Failure / surgery
  • Male
  • Models, Cardiovascular
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Myocardial Infarction / surgery
  • Nitric Oxide / pharmacology
  • Nitric Oxide / physiology
  • Organ Size / physiology
  • Rats
  • Rats, Wistar
  • Vasodilator Agents / pharmacology
  • Ventricular Pressure / physiology

Substances

  • Biological Factors
  • Vasodilator Agents
  • endothelium-dependent hyperpolarization factor
  • Nitric Oxide
  • Acetylcholine