Contribution of endogenous oxytocin to sodium excretion in anaesthetized, surgically operated rats

Abstract

In order to determine the possible role of endogenous oxytocin in controlling electrolyte and water excretion in animals whose renal function is being assessed by invasive techniques, rats were anaesthetized and subjected to micropuncture surgery. Clearance measurements were made in the presence and absence of the potent oxyto- 9 ]-vasotocin. In rats infused with vehicle alone, glomerular filtration rate (GFR), sodium excretion and urine flow rate remained stable. In contrast, in antagonisttreated rats GFR was modestly reduced (P<0·05), and there were large falls in both absolute and fractional sodium excretion (P<0·01 in each case) and absolute and fractional water excretion (P<0·05 in each case), indicating effects on both filtered load and fractional tubular reabsorption.The antinatriuresis was not accompanied by a change in the fractional excretion of lithium, suggesting that proximal tubular function is unaffected by oxytocin receptor antagonism; nor was it accompanied by a change in the fractional excretion of potassium, suggesting that the tubular effect is located beyond the potassium secretory site, i.e. downstream of the cortical collecting tubule.We conclude that circulating plasma concentrations of oxytocin during anaesthesia and moderate surgery are sufficient to enhance GFR and reduce fractional tubular sodium and water reabsorption. This has important implications for the interpretation of invasive studies such as micropuncture.

Selective Blockade of Oxytocin and Vasopressin V_1a Receptors in Anaesthetised Rats: Evidence that Activation of Oxytocin Receptors rather than V_1a Receptors Increases Sodium Excretion

“…With respect to oxytocin receptor blockade, the data concur with those found previously using a less selective oxytocin receptor antagonist [6]. However, they contrast markedly with the effects of previously used V 1a antagonists.…”

“…Finally, the rats were laparotomised. We have shown previously that this combination of procedures causes elevation of endogenous plasma concentrations of both vasopressin and oxytocin [6], values averaging 12 pmol·l –1 and 20 pmol·l –1 , respectively, 5 h after the completion of surgery. In the present study, measurements made at the end of the experiment in a random sample of rats (n = 6) confirmed these observations: the plasma vasopressin concentration was 13.8 ± 4.2 (mean ± SEM) pmol·l –1 and the plasma oxytocin concentration was 19.8 ± 3.0 pmol·l –1 .…”

“…Infusion of oxytocin into experimental animals leads to a dose-dependent natriuresis [1,2,3], while administration of oxytocin receptor antagonists to animals with moderately raised plasma oxytocin concentrations results in antinatriuresis [4,5,6]. With vasopressin, the situation is less straightforward: moderate-to-high doses of vasopressin are invariably natriuretic [7,8,9], but the effect of lower, more physiological doses is less predictable.…”

“…The oxytocin receptor antagonist desGly-NH 2 ,d(CH 2 ) 5 [D-Trp 2 ,Thr 4 ,Dap 5 ]OVT (where Dap = diaminopropionic acid) has no anti-V 1a activity, while the V 1a receptor antagonist d(CH 2 ) 5 [Tyr(Me) 2 ,Dab 5 ]AVP (where Dab = diaminobutyric acid) has no anti-oxytocin activity [21]. We administered these antagonists to anaesthetised, laparotomised rats, which have significantly raised plasma concentrations of both oxytocin and vasopressin [6]. In addition, information on the nephron segment(s) responsible for the antagonists’ actions was obtained by measurement of lithium clearance (C Li ) as an index of proximal tubular function [23].…”

Oxytocin Polyuria and Polydipsia is Blocked by NaCl Administration in Food‐Deprived Male Rats

“…Systemic administration of OT is also involved in the excretion of urine and body sodium (10)(11)(12)(13)(14)(15)(16)(17)(18)(19), via receptors in the kidney (11,15), producing an increase in the glomerular filtration rate (10) and a reduction in tubular Na + reabsorption (20). These natriuretic and diuretic effects are physiological processes closely linked to hypovolaemic thirst and sodium hunger (21)(22)(23)(24)(25)(26).…”