Renal haemodynamic and excretory responses to bradykinin in anaesthetized dogs.
1. Effects of bradykinin (BK) on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Renal arterial infusion of BK at doses of 5 or 50 ng/kg per min produced dose-dependent increases in renal blood flow (RBF), without affecting systemic arterial pressure or glomerular filtration rate. There were also significant and dose-dependent increases in urine flow (UF), urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) and decreases in urine osmolality during BK infusion. 3. Renal haemodynamic and excretory responses to the BK infusion were completely abolished by the simultaneous administration of Hoe 140 (icatibant, 100 ng/kg per min intrarenally), a selective BK B2-receptor antagonist. 4. In the presence of NG-nitro-L-arginine (NOARG; 40 micrograms/kg per min intrarenally), a nitric oxide (NO) synthase inhibitor, BK-induced renal vasodilative and natriuretic effects were markedly attenuated, although responses of UF and urine osmolality to BK remained unchanged. The water diuretic effect of BK was abolished in dogs given both NOARG and ibuprofen (12.5 mg/kg bolus injection plus 12.5 mg/kg per h of sustained infusion intravenously), a cyclooxygenase inhibitor. 5. These results clearly indicate that renal haemodynamic and excretory responses to BK were mediated exclusively by the B2-receptor. Renal vasodilative and natriuretic responses are mainly linked to NO generation, while both NO and prostaglandin biosynthesis are involved in the BK-induced water diuresis.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan. matumrh@oysun01.oups.ac.jp
Tadano
K
K
Yamasaki
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D014554:Urination / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; C065679:icatibant; D001920:Bradykinin; D007052:Ibuprofen