Role of nitric oxide in the antiarrhythmic effects of ischaemic preconditioning

There is a good deal of evidence that nitric oxide, most probably derived from endothelial cells, plays an important role in both the early and the delayed cardioprotective effects of ischaemic preconditioning, induced either by coronary artery occlusion, rapid cardiac or physical exercise. The evidence for the involvement of nitric oxide comes mainly from pharmacological studies in a canine model of ischaemic preconditioning which demonstrate that inhibition of nitric oxide generation leads to the loss of protection against ischaemia and reperfusion-induced ventricular arrhythmias. These studies suggest that both the early and the delayed antiarrhythmic effects of preconditioning result from the bradykinin-triggered release of nitric oxide from endothelial cells and that the protective effects of nitric oxide under these conditions are mediated through elevation of myocyte cGMP. This concept suggest that there is a "cross-talk" between coronary vascular cells and cardiac myocytes which leads to cardioprotection. The concept also suggest that under those conditions where endothelial dysfunction is evident, such as hypertension, atherosclerosis, diabetes and ventricular hypertrophy, the susceptibility of the myocardium to ischaemia is increased and that this is due, in part, to the reduced formation of nitric oxide and of other 'endogenous myocardial protective substances' derived from endothelial cells.