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

Abstract

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 Hypertension 1 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. In the current study, canine afferent and efferent arteriolar diameter responses of superficial and juxtamedullary nephrons were evaluated in vivo by intravital CCD camera videomicroscopy. As was demonstrated by this group in an earlier study,2 ARB treatment dilated afferent and efferent arterioles in the superficial and juxtamedullary regions. In the presence of the ARB, ACE inhibition resulted in a small dilation of the superficial efferent arteriole whereas it caused a much larger dilation of the juxtamedullary afferent and efferent arterioles. The renal vascular responses to ACE inhibition were dependent on activation of bradykinin receptors and the subsequent generation of NO. Nonetheless, a portion of the juxtamedullary afferent arteriolar dilator response to ACE inhibition was …