Administration of the V_1a receptor antagonist d(CH₂)₅[Tyr(Me)²]AVP to rats with high vasopressin levels reduces sodium excretion (Musabayane et al. 1997; Walter et al. 2000), suggesting that stimulation of V_1a receptors is natriuretic. However, this antagonist cross-reacts to some extent with oxytocin receptors (Chan et al. 2000), and oxytocin is known to increase sodium excretion (Forsling et al. 1994; Walter et al. 2001). In the present study we have used a recently developed, highly selective V_1a receptor antagonist to test the hypothesis that previous findings with the less selective analogue might have resulted from blockade of oxytocin receptors.

Male Sprague-Dawley rats were anaesthetized with Intraval (May & Baker; 100 mg kg^-1, I.P.), prepared for clearance studies and laparotomized, as described previously (Walter et al. 2001). After a 1 h control period, one group of animals (n = 10) received the V_1a antagonist d(CH₂)₅[Tyr(Me)², Dab⁵]AVP (Chan et al. 2000; 100 mg bolus, 50 mg h^-1; I.V.) for 2 h, while a time-control group (n = 10) continued to receive saline alone. This dose of antagonist had previously been shown to block the pressor effect of 10 mU of vasopressin. At the end of each experiment, the rat was killed with an overdose of Intraval. Table 1 shows glomerular filtration rate (GFR), sodium excretion (U_NaV) and fractional sodium excretion (FE_Na) during the control period and during the final hour of antagonist or vehicle infusion (experimental period). The V_1a antagonist had no significant effect on these variables; in particular, there was no evidence for a reduction in FE_Na.

These findings with a highly selective V_1a antagonist call into question previous claims that V_1a receptor stimulation is natriuretic.

The V_1a antagonist was a gift from Professor M. Manning.

All procedures accord with current UK legislation.