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

Angiotensin-converting enzyme (ACE) inhibitors, beside preventing angiotensin II (All) generation, inhibit the breakdown of kinins and thus increase plasma kinin levels. The potentation of kinins by ACE inhibitors explains part of their vascular actions, including acute and chronic antihypertensive effects and also their contribution to cardioprotective, antiatherosclerotic and antiproliferative action. Comparative studies on the effects of ACE inhibitors and specific All receptor antagonists on insulin resistance and fibrinolytic balance have suggested that potentation of the kinin system, rather than inhibition of the renin-angiotensin system, may also play an important role in the positive effects of ACE inhibitors on insulin sensitivity and fibrinolysis. Possible mechanisms whereby kinins may favourably influence insulin sensitivity include: (1) enhancement of insulin-stimulated peripheral glucose uptake through vasodilatation, increase in vascular permeability, prevention of vascular rarefaction; (2) acceleration of plasma glucose oxidation and; (3) reduction in endogenous glucose production. Prostaglandins and nitric oxide are the most likely second messengers of these effects of kinins. Furthermore, bradykinin is an important mediator of tissue plasminogen activator production at the level of the endothelial cells and plays an important role in the regulation of fibrinolytic balance. Given the link between insulin resistance and plasminogen activator inhibitor-1 levels, the positive effects of ACE inhibitors on fibrinolytic parameters might also be mediated by the above-mentioned improvement in insulin sensitivity.