The involvement of endogenous oxytocin (OT) in the renal natriuretic response to an intravenous load of hypertonic and isotonic saline was investigated in anesthetized male rats with use of a selective OT-receptor antagonist [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-OT (OT-ant). NaCl was infused (0.05 mmol.min-1.kg body wt-1 iv for 120 min) as a hypernatremic (HNa) solution or as an isotonic solution producing volume expansion (VE). HNa markedly increased sodium excretion from 0.25 +/- 0.06 to 10.04 +/- 0.62 mumol/min, whereas VE yielded only a moderate increase from 0.25 +/- 0.04 to 1.64 +/- 0.15 mumol/min. The increase in potassium excretion and urine flow rate during HNa was similar to that during VE. There were no significant changes in mean arterial pressure in either case. Administration of OT-ant delayed the natriuresis induced by HNa and reduced it by 60% but did not affect that induced by VE. Plasma OT concentration was significantly increased from 10.2 +/- 1.7 to 18.8 +/- 1.8 pg/ml at the end of HNa stimulation. In conclusion, the natriuresis in response to the intravenous sodium load was much more pronounced when NaCl was administered as a hypertonic solution than as an infusion inducing isotonic VE. Direct evidence was produced to assert that endogenous OT and its receptors are highly involved in the natriuresis elicited by systemic hypernatremic stimulation.

In a previous study in rats we demonstrated the existence of osmoregulatory natriuretic mechanisms distinct from the natriuretic mechanisms that are dependent on volume stimulation. At the same time, we found that oxytocin (OT) receptors were important mediators of natriuresis induced by hypernatremia but not of that induced by isotonic volume expansion. In the present study, the role of OT in dehydration natriuresis was examined in conscious rats. Dehydration for 24 h caused hypernatremia (from 142.1 +/- 0.4 to 147.7 +/- 0.7 mmol/l) and natriuresis accompanied by an approximately 30% spontaneous reduction of food intake. In conjunction with renal retention of water caused by an increase in circulating vasopressin, the natriuresis and probably the reduction of food intake can help to counteract the rise in body fluid osmolality. This natriuresis could not be fully explained by the reduction in plasma aldosterone. Plasma OT concentration had increased from 15.5 +/- 1.2 to 23.8 +/- 2.0 pg/ml at the end of 24 h of dehydration. Intravenous infusion of a selective OT-receptor antagonist [Mpa1,D-Tyr(Et)2, Thr4, Orn8]-OT using osmotic minipumps prevented dehydration natriuresis. It is concluded that in a dehydration-induced hypernatremic state OT is released, inducing natriuresis and facilitating sodium homeostasis. This mechanism is activated by Na osmoreceptors, but is not primarily dependent on the volume status.

To identify defects in the salt-sensitive Dahl rat (Dahl-S), the natriuretic, catecholaminergic and pressor responses to 60-min elevation of the cerebroventricular sodium concentration (CNS-induced natriuresis) were compared between prehypertensive salt-sensitive Dahl-S and salt-resistant Dahl rats (Dahl-R). The plasma concentrations of the rat natriuretic hormone oxytocin, which has implications for the development of hypertension, and vasopressin (AVP) were also measured. Basal sodium and catecholamine excretion and mean arterial blood pressure (MAP) were similar in both strains. Sodium excretion during CNS stimulation increased more than 15-fold in Dahl-R but only 10-fold in Dahl-S. Dopamine excretion increased only transiently and similarly in both strains. Noradrenaline excretion and response to CNS stimulation were similar, suggesting a comparable sympathetic nervous activity between the strains. MAP increased comparably in Dahl-R and Dahl-S. Plasma AVP concentration was similar in both strains while plasma oxytocin concentration after CNS stimulation was more than 2-fold higher in Dahl-S than in Dahl-R. In conclusion, the prehypertensive Dahl-S has an attenuated natriuretic response to elevations of the cerebroventricular fluid sodium concentration and a higher plasma level of the natriuretic hormone oxytocin. Dopamine is not a mediator of CNS-induced natriuresis in neither strain. The attenuated natriuretic response may partly explain the salt-sensitivity in Dahl-S, and the higher plasma oxytocin value may either represent an effort to compensate for the deficient natriuretic response or reflect a primary defect in this system. Due to the known involvement of oxytocin in central MAP regulation in some hypertensive animal models, the findings warrant further investigation.

The release of arginine‐vasopressin (AVP) and oxytocin (OT) from the rat neurointermediate lobe (NIL) of the pituitary was studied in vitro in the male spontaneously hypertensive rat (SHR) and the Wistar‐Kyoto rat (WKY). The basal and stimulated (50 mM KCl; a submaximal dose) release of AVP were significantly higher in the SHR than in the WKY. No corresponding strain difference was seen in OT release. In the WKY, depolarisation released more OT than AVP. The GABA–A agonist muscimol attenuated the KCl induced release of both peptides. The findings indicate that a lower dose of muscimol is required to inhibit the AVP than the OT release. It is concluded that the strain difference in AVP release does not apply to OT terminals, which indicates a difference in mechanisms regulating the AVP and OT release at the NIL level.