Renal haemodynamic effects of B2 receptor agonist bradykinin and B2 receptor antagonist HOE 140 in conscious lambs

The present study was designed to test the hypothesis that the high renal vascular resistance characteristic of the newborn results from age-dependent changes in the responsiveness of the renal vasculature to kinins. Two studies were carried out in conscious, chronically instrumented lambs aged 1 and 6 weeks. Firstly, we measured the renal blood flow response to intra-arterial injection of the B2 receptor agonist bradykinin over the range of doses 0-800 ng x kg(-1). The ED50 renal blood flow response to bradykinin was 50 ng x kg(-1) in both age groups of lambs. Secondly, we measured the effects of intravenous administration of 12.5 microg x kg(-1) of the specific B2 receptor antagonist HOE 140; this dose attenuated the renal blood flow response to 50 ng x kg(-1) of bradykinin in both age groups. HOE 140 administration was associated with an age-dependent increase in mean arterial pressure, with little effect on heart rate or renal vascular resistance. This study provides new information regarding the effects of kinins in modulating renal haemodynamics during postnatal maturation. We reject our hypothesis and conclude that the high renal vascular resistance of the newborn does not appear to result from age-dependent changes in the responsiveness of the renal vasculature to endogenous kinins.