Intrarenal bradykinin elicits reno-renal reflex sympatho-excitation and renal nerve-dependent fluid retention.

Abstract

The renal sensory nerves are importantly involved in the sympathetic regulation of cardiovascular and renal function. Two reno-renal reflexes are recognized, one in which activation of renal sensory nerves elicits a renal sympatho-inhibition, and one which causes a renal sympatho-excitation and about which little is known. This study investigated the role of bradykinin (BK) in engaging an excitatory reno-renal reflex. Rats were anaesthetized (chloralose/urethane) and prepared for the measurement of renal function or renal sympathetic nerve activity (RSNA). BK was infused into the cortico-medullary border of the ipsilateral kidney and the impact on contralateral renal function and RSNA evaluated. Intrarenal infusion of BK at 3 × 10(-9) and 6 × 10(-9) g L(-1) had no effect on mean arterial pressure, at 104 ± 5 mmHg or glomerular filtration rate in either the ipsilateral or contralateral kidneys, at 4.31 ± 0.45 mL min(-1) kg(-1) . At the highest dose of BK, fractional sodium excretion (FENa) was 1.47% in the ipsilateral kidney and was significantly lower, at 0.64% (P < 0.05) in the contralateral kidney but this difference did not occur following ipsilateral renal denervation. Ipsilateral intrarenal infusion of BK at 3 × 10(-9) , 6 × 10(-9) and 1.2 × 10(-8) g L(-1) elicited dose-related increases (P < 0.05) in contralateral RSNA, reaching some 78% at the highest dose, but these responses were prevented by ipsilateral renal denervation. Intrarenal infusion of BK produced an excitatory reno-renal reflex which was expressed as a renal nerve-dependent antinatriuresis in the contralateral kidney. The findings suggest that inflammatory mediators such as BK may be important in initiating a sympatho-excitation associated with renal and cardiovascular diseases.