The aim of the present study was to investigate the effects of experimental
diabetes and hyperglycaemia per se on the endothelium-dependent relaxation
of isolated canine coronary arteries and to analyse the possible involveme
nt of the cyclooxygenase pathway in the alterations induced by hyperglycaem
ia. Rings from the left anterior descending coronary arteries of 18 metabol
ically healthy, six alloxan-diabetic and six insulin-treated alloxan diabet
ic dogs were set up for isometric tension recording. Diabetic coronaries as
well as healthy vessels subjected to in vitro hyperglycaemia (25.5 mmol L-
1 glucose) showed impaired (P < 0.05) relaxation to acetylcholine (3 nmol L
-1-10 mu mol L-1) compared with normoglycaemic, i.e. metabolically healthy
and insulin-treated diabetic controls, either before or after indomethacin
(3 mu mol L-1) administration. The maximal dilation elicited by acetylcholi
ne was further decreased (P < 0.05) by the cyclooxygenase inhibitor in the
diabetic coronaries only. Relaxation to sodium nitroprusside did not differ
among groups. These results suggest that hyperglycaemia may result in impa
ired endothelium-dependent dilation of coronary arteries. Diminished relaxa
tion of diabetic coronaries is worsened by the inhibition of the synthesis
of vasodilator cyclooxygenase products.