Differential effects of endothelin-1 and big endothelin on canine kidneys.
Renal effects of endothelin-1 (ET-1, human, 1-21) and the equivalent molar concentration of big ET (human, 1-38) and the contributions of prostaglandins and endothelium-derived relaxing factor to these actions were examined. Intrarenal infusion of ET-1, at a dose of 0.4 pmol/kg/min, decreased renal blood flow (RBF), glomerular filtration rate (GFR), and urine output (V) to 62, 70, and 45% of control values, respectively. Additional aspirin-DL-lysine (ASP) treatment (25 mg/kg) caused marked decreases in RBF, GFR, and V to 20, 14, and 9% of control values, respectively. During ET-1 infusion, intrarenal infusion of NG-monomethyl-L-arginine (L-NMMA, 1 mumol/min) caused decreases in RBF, GFR, and V. In another group, intrarenal infusion of big ET at a dose equivalent to that of ET-1 did not significantly affect RBF, GFR, or urine output, which were 95, 107, and 84% of control values, respectively. Additional ASP treatment decreased these values to 78, 69, and 52% of control values, respectively. L-NMMA infusion during big ET infusion showed little effect on renal function. Our study demonstrated that intrarenal infusion of ET-1, at a dose of 0.4 pmol/kg/min, caused significant hemodynamic and functional changes in the canine kidney compared with an equivalent molar concentration of big ET.
Akabane
S
S
Research Institute, National Cardiovascular Center, Suita, Japan.
Yoshimi
H
H
Yoshida
K
K
Kawano
Y
Y
Ashida
T
T
Kinoshita
O
O
Matsushima
Y
Y
Kawamura
M
M
Imanishi
M
M
Kuramochi
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D019332:Endothelin-1; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D019323:omega-N-Methylarginine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019332:Endothelin-1; D016232:Endothelins; D011453:Prostaglandins; D011498:Protein Precursors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate