Effects of bradykinin on renal nerve stimulation-induced antidiuresis and norepinephrine overflow in anesthetized dogs.
We examined effects of bradykinin on antidiuresis and norepinephrine overflow induced by renal nerve stimulation (RNS) in anesthetized dogs, with or without blockade of the B2 receptor by Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]bradykinin) or the endogenous nitric oxide generation by N(G)nitro-L-arginine (NOARG), a nitric oxide synthase inhibitor. RNS (0.5-2.0 Hz) produced significant decreases in urine flow, urinary and fractional excretions of sodium, and increases in norepinephrine secretion rate (NESR), without affecting systemic and renal hemodynamics. Intrarenal arterial infusion of bradykinin (5 ng/kg per minute) significantly suppressed the RNS-induced antidiuresis and increase in NESR. Hoe 140 (100 ng/kg per minute) did not affect the RNS-induced renal actions, but in the presence of Hoe 140, bradykinin-induced suppressive actions on reductions in urine formation and increases in NESR in response to RNS were abolished. RNS during intrarenal arterial infusion of NOARG (40 microg/kg per minute) led to potent reductions in urine formation and decreased renal blood flow and glomerular filtration rate. Simultaneously, NESR was markedly increased. During NOARG infusion, bradykinin-induced decreases in renal actions elicited by RNS were markedly attenuated. These findings suggest that bradykinin suppresses the RNS-induced norepinephrine overflow and renal actions via nitric oxide production mediated by activation of B2 receptor. Renal noradrenergic neurotransmission may be inhibited by bradykinin at the prejunctional level, when its local production in the kidney is enhanced.
Tadano
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Yamasaki
T
T
Matsumura
Y
Y
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004285:Dogs; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D009318:Natriuresis; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects*; D014556:Urine
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; C065679:icatibant; D001920:Bradykinin; D009638:Norepinephrine