1 Anaesthetized, open-chest dogs were subjected to 60min of left circumflex coronary artery occlusion followed by 90min of reperfusion. Endothelium-dependent and -independent relaxant responses of the isolated coronary arterial rings were then investigated. 2 The endothelium-dependent, acetylcholine-induced relaxation of ischaemic/reperfused arterial rings was significantly attenuated in comparison to control rings (1.9 fold rightward shift, ischaemic/reperfused maximum relaxation = 57 + 13% of control maximum relaxation; P < 0.05). In contrast, glyceryl trinitrate produced similar relaxant responses in control and ischaemic rings.3 Pretreatment of dogs with either amlodipine (3 pgkg-1min-m, i.v.) or propranolol (1 mgkg-1, i.v.) completely prevented the postischaemic impairment of endothelium-dependent relaxant responses (100 + 3% and 90 + 5% of control maximum relaxation, respectively). 4 Allopurinol pretreatment (25mgkg-1, p.o. 24h previously, plus 50mgkg-1 i.v. 5min before arterial occlusion) partially protected against endothelial dysfunction by preventing the ischaemia-induced rightward shift of the acetylcholine relaxation curve and increasing the maximum relaxation response (83 + 7% of control rings). 5 These results confirm that endothelium-dependent coronary vascular relaxation is impaired by ischaemia and reperfusion, and that the ischaemia-induced impairment is reduced by pretreatment with amlodipine, propranolol or allopurinol.

1 We have assessed the effect of allopurinol, amlodipine and propranolol pretreatment on both endothelium-dependent and endothelium-independent coronary vasodilatation in vivo, by comparing pre-ischaemic responses with those measured after 60 min of coronary artery occlusion and 30 min of reperfusion in anaesthetized dogs. 2 In 15 untreated dogs ischaemia and reperfusion attenuated the increases in coronary blood flow produced by either acetylcholine (0.01-0.05ttg kg-', i.a.) or glyceryl trinitrate (0.05-0.2;Lg kg-', i.a.), to an average of 39 ± 4% and 42 ± 5% of the pre-ischaemic control response, respectively (both P <0.05).3 In 5 dogs treated with allopurinol (25 mg kg-', orally, 24 h previously, plus 50 mg kg-', i.v., 5 min before occlusion), the increases in coronary blood flow after ischaemia and reperfusion (acetylcholine: 78 ± 12%, glyceryl trinitrate: 60 ± 3% of pre-ischaemic response) were significantly larger than postischaemic responses in untreated dogs (both P <0.05). 4 Similarly, amlodipine treatment (3 fig kg Imin-', i.v., starting 90 min before occlusion) in 5 dogs improved post-ischaemic increases in blood flow (acetylcholine: 58.5%, glyceryl trinitrate: 66 ± 6% of pre-ischaemic response, significantly greater than post-ischaemic responses in untreated dogs, P <0.05). 5 In contrast, in a further 6 dogs pretreated with propranolol (1 mg kg-', i.v., 30 min before occlusion, plus 0.5 mg kg-' h-', i.v.), blood flow responses after ischaemia and reperfusion were not different from post-ischaemic responses in untreated dogs (acetylcholine: 46± 6%, glyceryl trinitrate: 46± 6% of pre-ischaemic response). 6 These results suggest that allopurinol and amlodipine protect against the post-ischaemic impairment of endothelium-dependent and endothelium-independent coronary vasodilatation in vivo by mechanisms additional to endothelial protection.