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(Hypertension. 2007;50:110.)
© 2007 American Heart Association, Inc.

Original Articles

Potentiation of Bradykinin Effect by Angiotensin-Converting Enzyme Inhibition Does Not Correlate With Angiotensin-Converting Enzyme Activity in the Rat Mesenteric Arteries

Disney O. Sivieri, Jr; Luiz B. Bispo-da-Silva; Eduardo B. Oliveira; Angela C. Resende; Maria Cristina O. Salgado

From the Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.

Correspondence to Maria Cristina O. Salgado, Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto-USP, 14049-900 Ribeirão Preto, São Paulo, Brazil. E-mail mcdosalg{at}fmrp.usp.br

Angiotensin-converting enzyme (kininase II [ACE]) inhibitors are capable of potentiating bradykinin (BK) effects by enhancing the actions of bradykinin on B₂ receptors independent of blocking its inactivation. To investigate further the importance of ACE kininase activity on BK-induced vasodilation, we investigated the effect of inhibiting ACE, as well as other kininases, on both BK metabolism and vasodilator effect in preparations that exhibit increased ACE activity. Mesenteric arterial beds obtained from 1-kidney, 1-clip hypertensive rats presented augmented ACE and angiotensin I converting activities compared with normotensive rats. The isolated and perfused mesenteric beds were exposed to BK for 15 minutes in the absence or in the presence of kininase inhibitors; then, the perfusate was collected for analysis of the products of BK metabolism by high-performance liquid chromatography. BK was metabolized to the fragments BK(1-8), BK(1-7), and BK(1-5), and the recovery of intact BK was reduced by 47% in the hypertensive group. Recovery of BK was increased in both groups in the presence of a kininase I inhibitor and in the hypertensive group by neutral endopeptidase 24.11 inhibitor; however, ACE inhibition did not affect BK metabolism in both groups. In contrast, only the ACE inhibitor potentiated the vasodilator effect of BK in a mesenteric bed preconstricted with phenylephrine; the increase in BK effect, nevertheless, was not greater in arteries from hypertensive rats that presented an increased ACE activity when compared with those in the normotensive group. These data demonstrated that ACE inhibitor–induced potentiation of BK vasodilator effects is not related to their actions on BK degradation.

Key Words: bradykinin • ACE activity • kininase I • endopeptidases • ACE inhibitor

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