High concentrations of oxytocin cause vasoconstriction by activating vasopressin V1A receptors in the isolated perfused rat kidney.
The aim of this study was to evaluate the renal vascular effects of oxytocin in Sprague-Dawley rats and in Brattleboro heterozygous or homozygous rats, the latter being genetically deficient in vasopressin synthesis. Studies were performed in vitro, in the isolated kidney perfused in an open circuit with a Tyrode's solution. Oxytocin induced a concentration-dependent renal vasoconstriction in Sprague-Dawley rats, at rather high concentrations (EC50=170+/-39 nM, mean +/- SEM, n=6) with a maximum response amounting to 44% of that elicited by vasopressin (increase in renal vascular resistance: 11.5+/-0.9 mmHg min ml(-1) vs. 26.2+/-2.2 mmHg min ml(-1)). Oxytocin-evoked renal vasoconstriction was abolished by SR 49059, a selective vasopressin V1A receptor antagonist (10 nM), but not by d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-(NH2)9] vasotocin, an oxytocin receptor antagonist (10 nM). In the presence of SR 49059, oxytocin did not induce renal vasorelaxation. Oxytocin induced renal vasoconstriction in Brattleboro homozygotes and heterozygotes (EC50=59+/-12 nM and 262+/-110 nM; Emax=7.8+/-1.1 mmHg min ml(-1) and 6.9+/-0.4 mmHg min ml(-1), n=5 respectively) with characteristics similar as observed in Sprague-Dawley rats concerning partial agonist activity, low potency and antagonism by SR 49059. Responsiveness to vasopressin did not differ in Brattleboro homozygotes and heterozygotes (EC50 approximately 0.25 nM) and was similar as we reported in Sprague-Dawley rats. These findings indicate that high concentrations of oxytocin induce renal vasoconstriction in the rat by activating vasopressin V1A receptors. The low agonist activity makes it unlikely that oxytocin can substitute functionally for vasopressin at the renal vascular V1A receptor in Brattleboro homozygous rats which are deficient in endogenous vasopressin.
Loichot
C
C
Institut de Pharmacologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Krieger
J P
JP
De Jong
W
W
Nisato
D
D
Imbs
J L
JL
Barthelmebs
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects*; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000172:deficiency / Q000494:pharmacology*
D017483:Receptors, Vasopressin; D014667:Vasopressins; D010121:Oxytocin