Endogenous Bradykinin Regulates Renal Function in the Newborn Rabbit

Abstract

The developmental changes in the activity of the renal kallikrein-kinin system (KKS) are related to the hemodynamic changes occurring in the neonatal kidney. In order to clarify the functional importance of the renal KKS in the developing kidney, the effect of the bradykinin B2 receptor antagonist HOE-140 was investigated in newborn rabbits. Effective blockade of bradykinin effect by HOE-140 was demonstrated in 10 rabbits. In 10 additional animals the subcutaneous injection of 300 µg/kg HOE-140 resulted in an increase in renal vascular resistance with a consequent decrease in renal blood flow. Glomerular filtration rate did not change significantly, while the filtration fraction rose, indicating preferential efferent arteriolar constriction. Urine flow rate increased as well as the fractional excretion of potassium. No change in sodium excretion was observed. The present data suggest a regulatory role for the renal KKS in the immature kidney under basal conditions. By inducing predominant efferent arteriolar vasodilation, the KKS appears to play a key role in regulating the neonatal glomerular microcirculation. This is in sharp contrast with the mature kidney, where the KKS predominantly acts on tubular function as a diuretic-natriuretic factor.

The Role of Bradykinin in Neonatal Hemodynamic Effects of ACE Inhibition

“…Another possible explanation is that BK has no role in neonatal blood pressure regulation. Previous results from our laboratory indeed indicate that endogenous BK has no systemic vasodilator influence in newborn rabbits [3].…”

“…This dose of BKA completely inhibits the BK-induced (300 ng/kg i.a.) hypotension for 3 h in newborn rabbits [3].…”

Bradykinin in the Newborn Kidney

“…Blockade of bradykinin B2 receptors by icatibant (300 µg/kg s.c. bolus) resulted in a very slight decrease in the systemic blood pressure [18]. This result excluded the vasodilating role of the peptide in the systemic circulation of the newborn under basal conditions.…”

“…Icatibant caused renal vasoconstriction in newborn rabbits, characterized by a 20% fall in renal blood flow, an increased filtration fraction, and no change in glomerular filtration (fig. 1) [18]. These changes could be explained by a preferential vasodilating effect of bradykinin on the efferent arterioles [19]or alternatively by its constricting effect on mesangial cells [20].…”

“…The higher neonatal expression of B2 receptors probably accounts for this difference. That bradykinin exerts a diuretic effect in the newborn was excluded in the study performed by Tóth-Heyn and Guignard [18]; the surprising diuretic effect of icatibant can be explained by its partial agonistic action.…”