Benefits of the bradykinins beyond blood pressure control: insulin sensitivity and thrombogenesis

,Angiotensin-converting enzyme (ACE) inhibitors, beside preventing angioten sin II (AII) generation, inhibit the breakdown of kinins and thus increase plasma kinin levels. The potentation of kinins by ACE inhibitors explains p art of their vascular actions, including acute and chronic antihypertensive effects and also their contribution to cardioprotective, antiatherosclerot ic and antiproliferative action. Comparative studies on the effects of ACE inhibitors and specific AII receptor antagonists on insulin resistance and fibrinolytic balance have suggested that potentation of the kinin system, r ather than inhibition of the renin-angiotensin system, may also play an imp ortant role in the positive effects of ACE inhibitors on insulin sensitivit y and fibrinolysis. Possible mechanisms whereby kinins may favourably influ ence insulin sensitivity include: (1) enhancement of insulin-stimulated per ipheral glucose uptake through vasodilatation, increase in vascular permeab ility, prevention of vascular rare fraction (2) acceleration of plasma gluc ose oxidation and; (3) reduction in endogenous glucose production. Prostagl andins and nitric oxide are the most likely second messengers of these effe cts of kinins. Furthermore, bradykinin is an important mediator of tissue p lasminogen activator production at the level of the endothelial cells and p lays an important role in the regulation of fibrinolytic balance. Given the link between insulin resistance and plasminogen activator inhibitor-1 leve ls, the positive effects of ACE inhibitors on fibrinolytic parameters might also be mediated by the above-mentioned improvement in insulin sensitivity .