Selective Blockade of Oxytocin and Vasopressin V1a Receptors in Anaesthetised Rats: Evidence that Activation of Oxytocin Receptors rather than V1a Receptors Increases Sodium Excretion
Background: Although it is known that moderate-to-high doses of the neurohypophysial hormones oxytocin and vasopressin are natriuretic, doubts remain over the identity of the receptors responsible. To address this issue, we have used highly selective antagonists of oxytocin and vasopressin receptors...
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Veröffentlicht in: | Nephron 2011-02, Vol.117 (3), p.p21-p26 |
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Sprache: | eng |
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Zusammenfassung: | Background: Although it is known that moderate-to-high doses of the neurohypophysial hormones oxytocin and vasopressin are natriuretic, doubts remain over the identity of the receptors responsible. To address this issue, we have used highly selective antagonists of oxytocin and vasopressin receptors in animals with elevated endogenous circulating levels of the 2 hormones. Methods: Rats were anaesthetised and prepared surgically for clearance studies, thereby raising plasma oxytocin and vasopressin concentrations. Sodium excretion, glomerular filtration rate and lithium clearance (an index of end-proximal fluid delivery) were measured: first during a control period, then after administration of the selective oxytocin receptor antagonist desGly-NH 2 ,d(CH 2 ) 5 [D-Trp 2 ,Thr 4 ,Dap 5 ]OVT, the selective vasopressin V 1a receptor antagonist d(CH 2 ) 5 [Tyr(Me) 2 ,Dab 5 ]AVP, or vehicle alone. Results: Absolute and fractional sodium excretion fell in rats given the oxytocin antagonist (by 32 and 27%, respectively, compared with corresponding values in vehicle-infused rats), but not in those given the V 1a antagonist or vehicle. Antinatriuresis was associated with a small reduction in the ratio of sodium clearance to lithium clearance (an index of the fraction of distally delivered sodium that escapes reabsorption in the distal nephron). Conclusions: These results corroborate previous studies showing that activation of oxytocin receptors increases sodium excretion and imply that the natriuretic effect of elevated plasma vasopressin concentrations results from stimulation of oxytocin receptors. |
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ISSN: | 1660-2137 1660-8151 1660-2137 2235-3186 |
DOI: | 10.1159/000320290 |