Effects of bradykinin on renal nerve stimulation-induced antidiuresis and norepinephrine overflow in anesthetized dogs

We examined effects of bradykinin on antidiuresis and norepinephrine overfl ow induced by renal nerve stimulation (RNS) in anesthetized dogs, with or w ithout blockade of the B-2 receptor by Hoe 140 (D-Arg-[Hyp(3), Thi(5), D-Ti c(7), Oic(8)]bradykinin) or the endogenous nitric oxide generation by N-G-n itro-L-arginine (NOARG), a nitric oxide synthase inhibitor. RNS (0.5-2.0 Hz ) produced significant decreases in urine flow, urinary and fractional excr etions of sodium, and increases in norepinephrine secretion rate (NESR), wi thout affecting systemic and renal hemodynamics, Intrarenal arterial infusi on of bradykinin (5 ng/kg per minute) significantly suppressed the RNS-indu ced antidiuresis and increase in NESR. Hoe 140 (100 ng/kg per minute) did n ot affect the RNS-induced renal actions, but in the presence of Hoe 140, br adykinin-induced suppressive actions on reductions in urine formation and i ncreases in NESR in response to RNS were abolished. RNS during intrarenal a rterial infusion of NOARG (40 mug/kg per minute) led to potent reductions i n urine formation and decreased renal blood flow and glomerular filtration rate. Simultaneously, NESR was markedly increased. During NOARG infusion, b radykinin-induced decreases in renal actions elicited by RNS were markedly attenuated. These findings suggest that bradykinin suppresses the RNS-induc ed norepinephrine overflow and renal actions via nitric oxide production me diated by activation of B-2 receptor. Renal noradrenergic neurotransmission may be inhibited by bradykinin at the prejunctional level, when its local production in the kidney is enhanced.