Effects of NG-nitro-L-arginine on renal hemodynamic responses to endothelin-3 in anesthetized dogs.
The effects of NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, on renal vascular response to endothelin-3 (ET-3) were studied in anesthetized dogs. Intrarenal arterial (i.r.a.) infusion of ET-3 (5 and 25 ng/kg/min for 2 min) elicited a dose-dependent increase in renal blood flow (RBF) with no change in the systemic blood pressure (BP). Marked attenuation of the renal vasodilatory response to ET-3 was observed following the administration of L-NNA (75 micrograms/kg/min i.r.a. for 20 min), and there was a partial reversion when L-arginine (100 mg/kg i.v.) was given. Continuous administration of ET-3 at a rate of 5 ng/kg/min i.r.a. for 25 min increased RBF with no change in BP and heart rate (HR). The glomerular filtration rate (GFR) remained unchanged throughout the experiment, the result being a significant decrease in the filtration fraction (FF). The significant increase in urine flow rate (UF) was associated with a marked reduction in urine osmolarity (Uosm) during ET-3 infusion, but urinary excretion of sodium (UNaV) remained unchanged. Pretreatment with L-NNA abolished the ET-3-induced renal vasodilation. RBF decreased immediately after the start of ET-3 infusion into animals treated with L-NNA. Thus, ET-3 is a diuretic and renal vasodilatory peptide, the vascular effects of which may be mediated by production of endothelial NO in the kidney.
Yamashita
Y
Y
Department of Pharmacology, Osaka City University Medical School, Japan.
Yukimura
T
T
Miura
K
K
Okumura
M
M
Yamanaka
S
S
Yamamoto
K
K
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D019335:Nitroarginine; D012079:Renal Circulation / Q000187:drug effects*; D014563:Urodynamics / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D019335:Nitroarginine; D001120:Arginine