The Role of Bradykinin in Neonatal Hemodynamic Effects of ACE Inhibition

Abstract

Angiotensin-converting enzyme (ACE) inhibitors exert their effects by inhibiting angiotensin II (AII) production, but also by inhibiting bradykinin (BK) degradation. In order to clarify whether BK is involved in the systemic effects of ACE inhibition in the newborn period, we investigated the effect of perindoprilat (20 μg/kg i.v.) in newborn rabbits, with or without the blockade of BK β₂-receptors (Hoe 140, 300 μg/kg s.c.). The bolus infusion of perindoprilat resulted in a marked fall in mean arterial blood pressure (MBP) and a slight decrease in heart rate. BK receptor blockade had no effect on the perindoprilat-induced hypotension but the negative chronotropic effect of ACE inhibition was partly prevented by pretreatment with Hoe 140. We therefore conclude that BK is not involved in neonatal blood pressure regulation but that the ACE inhibition-induced neonatal bradycardia is at least partly BK- mediated.

The Effects of Losartan on Renal Function in the Newborn Rabbit

“…Addition of the NO synthase inhibitor N -nitro-L-arginine methyl ester to PD 123319 completely blunted the AII-mediated increases in cGMP without potentiation of PD 123319 inhibition by Nnitro-L-arginine methyl ester, suggesting that all of the cGMP production via AII stimulation of AT 2 could be accounted for by increased NO production (22). AT 2 stimulation is also directly linked to BK release (19,23). Studies in genetically engineered mice lacking AT 2 have confirmed the concept that AT 2 mediates a BK-NO-cGMP vasodilator cascade (18).…”