Influence of experimental diabetes on the mechanical responses of canine coronary arteries: Role of endothelium

Debebe Gebremedhin, Mária Zsófia Koltai, Gábor Pogátsa, K. Magyar, Pál Hadházy

Research output: Contribution to journalReview article

30 Citations (Scopus)

Abstract

The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol·kg-1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate solution for isometric recording. Relaxation responses to acetycholine (1.8 × 10-8 to 9.4 × 10-6 mol·litre-1, A23187 (10-8 to 1.28 × 10-6 mol·litre-1), and sodium nitroprusside (10-9 to 10-7 mol·litre-1) as well as contractile responses to prostaglandin F2a, (1.7 × 10-7to5.6 × 10-4 mol·litre-1) were determined. In all intact strips acetycholine, and A23187 induced similar concentration dependent reduction of the prostaglandin F (2 × 106 mol·litre-1) evoked tone. No significant difference was observed between sodium nitroprusside evoked relaxations of normal and diabetic arteries. Cyclooxygenase blockade reduced the maximal relaxations induced by acetylcholine and A23187 in diabetic vessels, whereas it did not change die endothelium dependent relaxation of normal arteries. Diabetes increased significantly the sensitivity to acetycholine (EC50 4.1(0.4) × 10-7 mol·litre-1 in control and 6(0.7) × 10-8 mol·litre-1 in diabetic arteries; p<0.01, n = 7) and to A23187 (EC50:7(1) × 10-8 mol·litre-1 in control and 3.8(0.3) × 10-8 mol·litre-1 in diabetic vessels; p<0.01, n=7); in contrast, prostaglandin F remained an equiactive constrictor in normal and diabetic vessels with intact endothelium. Endothelium removal abolished the relaxation responses to acetycholine and A23187 and considerably (p<0.05) increased the maximal contractile responses to prostaglandin F. The maximum tension induced by prostaglandin F was greater in diabetic denuded arteries (1.82(0.02) × 104 N·m-2) than in non-diabetic denuded vessels (1.25(0.04) × 104 N·m-2; p<0.05, n=7). These results indicate that experimental diabetes leads to impaired response to endothelium derived relaxing factor and a non-specific increase in maximal response of canine coronary arterial smooth muscle to prostaglandin F. They further suggest that the maintenance of sufficient relaxation capacity of diabetic dog coronary arteries requires the integrated operation of both endothelium derived relaxing factor and cyclooxygenase products (probably prostacyclin).

Original languageEnglish
Pages (from-to)537-544
Number of pages8
JournalCardiovascular Research
Volume22
Issue number8
DOIs
Publication statusPublished - Jan 1 1988

Keywords

  • A23187
  • Acetylcholine
  • Coronary artery
  • Diabetes
  • Endothelium
  • Prostaglandin F2α
  • Sodium nitroprusside

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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