High concentrations of oxytocin cause vasoconstriction by activating vasopressin V 1A receptors in the isolated perfused rat kidney

Abstract

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.

Oxytocin-Gly-Lys-Arg: A Novel Cardiomyogenic Peptide

“…The clinical application of OT-GKR in this pathology could be safe because of the specific interaction with OTR and V1aR, as described in the present study. The weaker effects of OT-X than OT on uterine contractions have already been reported [45], and OT replacement by OT-GKR in the therapy of cardiac pathologies could reduce vasoconstriction attributed to V1aR activation by OT [46].…”

Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

“…In previous studies reported in the literature, Oxytocin has been shown to play an important role in the regulation of the vascular compartment: it causes vasodilatation in the pre-constricted pulmonary vasculature [23] and induces renal vasoconstriction in rats by activating vasopressin V1A receptors [24]. Moreover, pharmacological studies have shown the existence of Oxytocin receptors in human umbilical vein endothelial cells (HUVEC); the interaction between Oxytocin and its receptor causes Figure 3.…”

Neurohypophyseal response to fluid resuscitation with hypertonic saline during septic shock in rats

“…Oxytocin also stimulates renin secretion, perhaps by an increase in the renal sympathetic nerve activity (Huang et al 2000). Additionally, in homozygous Brattleboro rats that are genetically deficient in endogenous vasopressin, oxytocin elicited V 1a receptor‐mediated renal vasoconstriction, in which oxytocin acted as a partial agonist with a low apparent potency (Loichot et al 2001). The blood volume expansion in response to HS during experimental septic shock induced by CLP stimulated oxytocin secretion, but the administration of the oxytocin receptor antagonist did not alter the pressor response, suggesting that oxytocin does not participate in this response.…”