[Role of endothelium-derived nitric oxide in mediating the natriuretic response to acute extracellular volume expansion].
To determine the role of endothelium-derived nitric oxide (EDNO) in mediating the natriuretic response to acute extracellular volume expansion (ECVE) with isotonic saline (3% of body weight per hour), the diuretic and natriuretic responses to ECVE were studied in anesthetized Sprague-Dawley rats during the intravenous infusion of an EDNO synthesis inhibitor, NW-nitro-L-arginine methyl ester (L-NAME). Intravenous infusion of L-NAME at the dose of 5 micrograms/kg/min significantly inhibited the diuresis and natriuresis in response to ECVE by 58% and 67%, without altering arterial pressure, effective renal plasma flow, glomerular filtration rate and basal excretory function. This inhibitory effect of L-NAME on the diuretic and natriuretic responses to ECVE was attenuated by the infusion of the EDNO synthesis precursor, L-arginine (1mg/kg/min), but not by D-arginine. In addition, pretreatment with 0.3 mg/kg of the angiotensin II receptor antagonist, L-158,809, normalized the diuretic and natriuretic responses to ECVE in L-NAME-treated rats, suggesting an angiotensin-II-dependency of the reduced renal excretory response to ECVE during EDNO synthesis inhibition. Neither L-arginine nor L-158,809 alone significantly altered the renal excretory response to ECVE compared with vehicle-treated control rats. These results suggest that EDNO might play an important role in the regulation of sodium and water excretion during ECVE, and indicate a possible interaction between EDNO and angiotensin II on the renal excretory function.
Fujioka
H
H
Second Department of Internal Medicine, Kagawa Medical School, Japan.
Fujita
Y
Y
Syoji
T
T
Uchida
K
K
Takahashi
N
N
Sumikura
T
T
Yuasa
S
S
Matsuo
H
H
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005110:Extracellular Space / Q000502:physiology*; D007552:Isotonic Solutions; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage
D007552:Isotonic Solutions; D000804:Angiotensin II; D009569:Nitric Oxide; D012965:Sodium Chloride; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester