Effects of EXP3174, a non-peptide angiotensin II receptor antagonist, on renal hemodynamics and renal function in dogs.
We examined the effects of intrarenal infusion of EXP3174, a non-peptide angiotensin II receptor antagonist, in order to evaluate the physiological role of endogenous angiotensin II in regulating renal hemodynamics and urine formation and to assess the possibility of a tubular site(s) of action of endogenous angiotensin II in anesthetized dogs. Intrarenal infusion of EXP3174 at 15 micrograms/kg per min caused increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine, flow and urinary electrolyte excretion. The lower dose of EXP3174 (0.5 micrograms/kg per min) did not change mean arterial pressure, RBF and GFR, but did increase urine flow. The fractional excretion of sodium, the fractional proximal excretion of sodium and the fractional distal excretion of sodium increased with lower doses of EXP3174 infusion. EXP3174 did not affect the linear relationship between the free water reabsorption rate and osmolar clearance. These data suggest that endogenous angiotensin II plays a significant role in regulating renal hemodynamics and urine formation and endogenous angiotensin II stimulates sodium reabsorption in the proximal and the distal portions of the tubules, with the exception of the medullary portion of the ascending limb of Henle.
Tamaki
T
T
Department of Pharmacology, Kagawa Medical School, Japan.
Nishiyama
A
A
Yoshida
H
H
He
H
H
Fukui
T
T
Yamamoto
A
A
Aki
Y
Y
Kimura
S
S
Iwao
H
H
Miyatake
A
A
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D019808:Losartan; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D012964:Sodium; C066026:losartan carboxylic acid; D019808:Losartan