Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC278
Bradykinin mediated activation of sensory nerves in the kidney: impact on contra-lateral kidney function
E. Barry1, E. J. Johns1
1. Department of Physiology, University College Cork, Cork, Ireland.
A body of evidence from both experimental and clinical studies has shown that renal injury or failure initiates a neural signal from the kidneys resulting in a sympatho-excitation and a rise in blood pressure (Campese VM et al. 2006). The mechanisms underlying this excitatory reflex are unclear and was investigated in two ways; firstly by stimulating the sensory nerves of one kidney with the inflammatory mediator, bradykinin (BK), and determining the impact on haemodynamic and excretory function of the contra-lateral kidney; secondly, by evaluating the contribution of the renal sensory nerves by removing their influence. Anaesthesia was induced in male Wistar rats using 1.2 ml chloralose/urethane (16.5/250mg/ml) IP. Cannulae were placed in a femoral artery, to monitor mean arterial pressure (MAP), and vein, for infusion of saline at 3ml/h containing inulin. The right and left kidneys were exposed, their ureters cannulated for urine collection and a small cannula inserted 4.0-4.5 mm into the cortico-medullary border of the left kidney for the infusion of saline and BK at a concentration of 3x10-6 or 6x10-6g/l at 1 ml/h. After 1.5h, 20 min clearances were taken, two before and two 15 min after the start of the BK infusions. Two groups were studied, one in which the renal sympathetic nerves to the left kidney were intact (n=7), and a second (n=6) in which they were disrupted by bathing with 10% phenol. The rats were killed at the end of the experiment. Data, means±SEM were subjected to ANOVA and significance taken at P<0.05. Intrarenal infusion of both doses of BK had no effect on MAP, at 107±6mmHg or glomerular filtration rate (GFR) in either left or right kidney, at 2.58±0.50 and 3.53±0.97ml/min/kg, respectively. The lower dose of BK had no effect on fractional sodium excretion (FENa) in either left or right kidneys, at 1.07±0.26% and 0.93±0.37%, respectively, and while the higher dose had little effect on FENa in the left kidney it was decreased (P<0.05) by 38% in the right kidney. Denervation of the left kidney had no effect on MAP or GFR but increased (P<0.05) FENa by 33% from that kidney. FENa did not change in either kidney when BK at low or high dose was infused into the left kidney. These findings showed that infusion of BK into the renal interstitium whilst having minimal effects on renal haemodynamics or fluid handling of that kidney, elicited a contra-lateral antinatriuresis which was prevented by an ipsi-lateral renal denervation. They suggest that an inflammatory mediator, BK, activates sensory nerves of that kidney causing an increase in sympathetic outflow which at the contralateral kidney results in sodium retention.
Where applicable, experiments conform with Society ethical requirements