Mild type 2 diabetes mellitus improves remote endothelial dysfunction after acute myocardial infarction

J Diabetes Complications. 2015 Nov-Dec;29(8):1253-60. doi: 10.1016/j.jdiacomp.2015.06.012. Epub 2015 Jul 2.

Abstract

Aims: Myocardial infarction (MI) is a common cause of mortality in patients with diabetes mellitus (DM) and vascular dysfunction is a major component of diabetic cardiomyopathy. We investigated the systemic influence of acute MI on the diabetes-induced pathogenic changes in the rat aorta.

Methods: Nondiabetic Wistar (W) and type-2 diabetic Goto-Kakizaki (GK) rats underwent 45min of left anterior descending coronary artery occlusion followed by 24h of reperfusion. Isometric force was measured using organ bath.

Results: Plasma glucose-levels were significantly higher in diabetic rats (GK+sham: 13±2mM; GK+MI: 19±2mM) compared to nondiabetic rats (W+sham: 8±0mM; W+MI: 8±1mM). Acetylcholine-induced relaxation was significantly weaker in rings from W+MI and GK+MI rats compared to corresponding sham-operated animals. Myocardial reperfusion injury was smaller in GK+MI than W+MI rats, and the concentration-response curves to acetylcholine were significantly enhanced in rings from GK+MI than W+MI rats. Nevertheless, the relaxation response to acetylcholine was similar in W+sham and GK+sham. Densitometric analysis of bands for endothelial nitric oxide synthase showed a significant decrease in W+MI rats compared to W+sham and GK+sham animals. Aortas from both GK+sham and GK+MI rats showed impaired contractile responses to phenylephrine in comparison with the nondiabetics.

Conclusions: For the first time we showed that short-term and mild type-2 DM improved remote endothelial dysfunction after reperfused acute MI.

Keywords: Acute Myocardial Dysfunction; Aorta; Contractile Response; Endothelial Dysfunction; Type 2 Diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / complications*
  • Diabetic Angiopathies / physiopathology
  • Diabetic Cardiomyopathies / complications*
  • Diabetic Cardiomyopathies / physiopathology
  • Disease Resistance
  • Drug Resistance
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Male
  • Myocardial Infarction / complications*
  • Myocardial Infarction / physiopathology
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / prevention & control*
  • Nitric Oxide Synthase Type III / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Inbred Strains
  • Rats, Wistar
  • Vasoconstriction / drug effects
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Blood Glucose
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat