[New perspectives for bradykinin in nephroprotection]

Abstract

Various diseases such as arterial hypertension, diabetes and obesity result in renal diseases which are often irreversible and resistant to currently available therapies. Beside the control of glycemia in diabetic patients, only the blockade of the renin-angiotensin system is effective in reducing the occurrence of glomerulosclerosis and its development towards terminal renal failure. Inhibition of this system is based on the use of angiotensin-1 converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor antagonists. For many years, the beneficial effects of these two classes of drugs were attributed mainly to their interference with angiotensin II. However, recent in vitro and in vivo evidences strongly suggest that bradykinin B2 receptor is also involved in the nephroprotective effects of these drugs. A compelling evidence is the finding that the development of glomerulosclerosis is more severe in knock-out B2 receptor mice. The nephroprotective effect of B2 receptor could be the consequence of a reduction of proteinuria, glomerular and interstitial fibrosis, cell proliferation and of the oxidative stress through the contribution of several well identified mechanisms. It is proposed that B2 receptor agonists can offer a novel therapeutic avenue in the treatment of nephropathies associated with diabetes or other vascular diseases.