Selective blockade of oxytocin receptors reduces sodium excretion in anaesthetized rats

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University of Sheffield (2001) J Physiol 535P, S084

Communications: Selective blockade of oxytocin receptors reduces sodium excretion in anaesthetized rats

M.F. Walter, B.D. Keeler, N.J. Waters, S.J. Walter and D.G. Shirley*

Division of Biomedical Sciences, Imperial College School of Medicine, London SW7 2AZ and * Centre for Nephrology, Royal Free & University College Medical School, London W1N 8AA, UK

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In previous studies, we and others have shown that oxytocin antagonists can reduce sodium excretion in animals with moderately raised plasma concentrations of oxytocin (Windle et al. 1997; Walter et al. 2000a). However, since the oxytocin antagonists used are not completely selective but bind also to vasopressin V1a receptors, and since blockade of V1a receptors has been shown to reduce sodium excretion (Walter et al. 2000b), the receptor type responsible for the antinatriuresis is uncertain. The present study has addressed this issue by using a recently developed, selective oxytocin receptor antagonist that has no cross reactivity with V1a receptors (Chan et al. 2000).

Male Sprague-Dawley rats were anaesthetized with Intraval (May & Baker; 100 mg kg-1, I.P.), venous and arterial cannulae were implanted, a laparotomy was performed, and the bladder catheterized. All rats were infused with 0.9 % NaCl solution at 4 ml h-1. After a 1 h control period, one group of animals (n = 8) received the oxytocin antagonist desGly-NH2,d(CH2)5[D-Trp2,Thr4,Dap5]OVT (Chan et al. 2000; 25 µg bolus, 12.5 µg h-1, I.V.) for 2 h, while a time-control group (n = 8) continued to receive saline alone. At the end of each experiment, the rat was killed with an overdose of Intraval. Table 1 shows glomerular filtration rate (GFR), sodium excretion (UNaV) and fractional sodium excretion (FENa) during the control period and during the final hour of antagonist or vehicle infusion (experimental period). The oxytocin antagonist caused significant reductions in both UNaV and FENa.

These findings indicate that selective blockade of oxytocin receptors results in modest reductions in absolute and fractional sodium excretion in anaesthetized, laparotomized rats; the effect is independent of V1a receptors.

The oxytocin antagonist was a gift from Professor M. Manning.

    Chan, W.Y., Wo, N.C., Stoev, S., Cheng, L.L. & Manning, M. (2000). Exp. Physiol. 85S, 7-18S.

    Walter, M.F., Forsling, M.L. & Shirley, D.G. (2000a). J. Endocrinol. 165, 19-24.

    Walter, M.F., Margono, J., Dindyal, S., Walter, S.J. & Shirley, D.G. (2000b). J. Physiol. 527.P, 11-12P.

    Windle, R.J., Judah, J.M. & Forsling, M.L. (1997). J. Endocrinol. 152, 257-264.

Where applicable, experiments conform with Society ethical requirements.

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