Allopurinol and amlodipine improve coronary vasodilatation after myocardial ischaemia and reperfusion in anaesthetized dogs

Abstract

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.

Oxidation by trace Cu2+ ions underlies the ability of ascorbate to induce vascular dysfunction in the rat perfused mesentery

“…These potential sources were excluded, however, because the NADPH oxidase inhibitor, diphenyleneiodonium ( Lassegue and Clempus, 2003 ), and the mitochondrial inhibitors, rotenone or myxothiazole ( Weir et al, 1991; Griffith et al, 1987 ), failed to protect EDHF-induced dilatation from blockade by ascorbate. Xanthine oxidase too was ruled out as the source of superoxide/hydrogen because allopurinol ( Sobey et al, 1993 ) failed to protect EDHF-induced dilatation. Nitric oxide synthase and cyclooxygenase were also excluded as sources since our experiments were routinely conducted in the presence of L-NAME and indomethacin.…”

Allopurinol Normalizes Endothelial Dysfunction in Type 2 Diabetics With Mild Hypertension

“…24 Allopurinol has been shown to reduce ventricular arrhythmia and to improve coronary artery blood flow, 25 to improve endothelial dysfunction, 26 and to reduce MDA levels 6 in animal studies. In humans, allopurinol has been investigated in coronary artery bypass graft surgery, where it has reduced ischemic events, produced less ST-T segment depression, and lowered the use of postoperative inotropic support.…”

The Effects of Calcium Channel Antagonists on Coronary Nitrite Outflow in Isolated Rat Heart

“…There is growing evidence that some Ca 2+ channel antagonists may have antioxidant effects and/or stimulate NO production [16,17,18]. Shear stress seems to be the most important factor regulating endothelial nitric oxide synthase activity and NO release.…”