ACE Inhibition and Bradykinin-Mediated Renal Vascular Responses: EDHF Involvement.

Angiotensin-converting enzyme (ACE) is known to catalyze the conversion of angiotensin I to angiotensin II and degrades bradykinin and other vasoactive peptides. The fact that ACE participates in the degradation of bradykinin has led to the postulate that the beneficial renal and cardiovascular actions of ACE inhibitors can be attributed to augmenting and prolonging the effects of bradykinin. These beneficial actions have been attributed to bradykinin stimulation of nitric oxide (NO) generation. The report by Matsuda et al in this issue of Hypertension1 provides initial evidence that the renal hemodynamic change in response to ACE inhibition and elevated bradykinin levels is also mediated by an endothelium-derived hyperpolarizing factor (EDHF). In addition, this renal vascular action of ACE inhibition provides greater hemodynamic and natriuretic effects in the presence of angiotensin type 1 receptor blockers (ARBs). Does this finding suggest that ACE inhibitors have yet another additional renal and cardiovascular beneficial effect not associated with ARBs? Thus, the debate regarding the renal and cardiovascular benefits of ACE inhibitors, ARBs, or combined therapy now includes the possible involvement of EDHF.