Effect of oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin in the rat.
The effect of three oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin was investigated in conscious male rats infused with hypotonic saline. Infusion of oxytocin at 100 pg/min produced plasma concentrations of 12.7 +/- 3.3 pmol/l and led to significant increases in sodium excretion, urine flow and glomerular filtration rate (GFR). The increase in sodium excretion of 42 +/- 9% during oxytocin infusion was significantly decreased by all three antagonists to 15 +/- 5% (10 ng [mercapto-proprionic acid1, D-Tyr(Et)2,Thr4,Orn8]-oxytocin/min), 13 +/- 5% (5 ng desGly9[D-Trp2,Thr4,Orn8]-dC6oxytocin/min) and 4 +/- 5% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). Similarly, the increase in urine production of 22 +/- 5% associated with oxytocin infusion was significantly decreased to 4 +/- 3% (5 ng desGly9[D-Trp2,D-Thr4,Orn8]-dC6 oxytocin/min) and 1 +/- 4% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/ min). All three antagonists blocked the oxytocin-induced increase in GFR when infused at 10 ng/min. Infusion of vasopressin at 160 pg/min produced plasma concentrations of 10.1 +/- 2.1 pmol/l and this led to a significant increase in sodium excretion and a significant decrease in urine flow rate. None of the antagonists had any effect on the natriuretic or antidiuretic actions of vasopressin suggesting that different receptors are involved in these renal actions of the two peptides.
Windle
R J
RJ
Department of Obstetrics and Gynaecology, United Medical Schools, London, UK.
Judah
J M
JM
Forsling
M L
ML
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors*; D014554:Urination / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
C055830:KB 5-21; D018045:Receptors, Oxytocin; D014667:Vasopressins; C076093:vasotocin, (beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-O-methyl-Tyr(2)-Thr(4)-Orn(8)-Tyr(9)-NH2; D010121:Oxytocin; C042951:oxytocin,1-(beta-mercapto-(beta, beta-cyclopentamethylene)propionic acid)-Tyr(OMe)(2)-Orn(8)-; D014668:Vasotocin