Influence of Oxytocin on Renal Hemodynamics and Sodium Excretion^a

Abstract

Acute administration of physiological doses of synthetic OT to conscious Long-Evans and Brattleboro homozygous diabetes insipidus rats produced a modest increase in GFR and effective filtration fraction. Chronic administration of OT to DI rats for 9 days in dosages that were antidiuretic (plasma OT ca. 100 pg/ml) increased both GFR and ERPF by 40%. Table 1 summarizes these renal hemodynamic changes and compares them to the renal effects of VP. Further investigation is needed to define the mechanisms responsible for the changes in GFR and/or ERPF produced by acute and chronic administration of OT to conscious rats. Acute administration of physiological doses of synthetic OT to conscious LE and DI rats also produced a brisk natriuresis with a marked increase in the fractional excretion of sodium. A natriuresis was also observed in conscious Sprague-Dawley rats administered physiological amounts of OT by subcutaneous osmotic minipump. The natriuretic effect of the hormone was short lived, however, being observed only during the first 24-hr period of treatment. The nephron site where OT exerts its natriuretic action, either directly or indirectly, is unknown. Renal prostaglandins may contribute to OT-induced natriuresis, but other mechanisms such as increased renal production of nitric oxide and cGMP have not been tested. Although the natriuretic response to OT has also been described for conscious dogs, it probably does not occur in humans and nonhuman primates. Precise localization of specific renal OT receptors has recently been reported for the rat. OT receptors were identified in the macula densa cells of the adult, rat kidney. This location suggests a possible role for OT in the regulation of tubuloglomerular feedback and solute transport. The signal transduction of the renal OT receptor has been recently evaluated in various kidney epithelial cells in culture. OT stimulates phosphoinositide hydrolysis and increases cytosolic calcium concentrations. In fact, VP produces similar cellular responses in renal epithelia, possibly through the OT receptor. Also, OT stimulates soluble guanylate cyclase and increases intracellular cGMP. Whether OT activates soluble guanylate cyclase secondarily through the production of nitric oxide has not been tested. An important role for OT in renal sodium homeostasis under basal conditions is likely, at least for the rat. Moreover, OT possibly mediates dehydration natriuresis in lower animal species. The contribution of OT to renal physiology in humans and in nonhuman primates, if any, remains uncertain.

Oxytocin is a cardiovascular hormone

“…The acute renal actions of OT include increased GFR, filtration fraction and sodium excretion without affecting potassium excretion (17) in Brattleboro rats with a hereditary lack of AVP (18), which suggests that OT exerts renal actions independent of vasopressin. Oxytocin also has tubular actions (19) on apical sodium conductance that may be related to increases in intracellular [Ca 2+ ] and cAMP production (20).…”

Synaptic control of rat supraoptic neurones during osmotic stimulation of the organum vasculosum lamina terminalis in vitro.

“…In the rat, these hormones promote water reabsorption (McDonald, Miller, Anderson, Berl & Schrier, 1976) and sodium excretion (Conrad, Gellai, North & Valtin, 1993) by the kidney. Both hormones, therefore, have been proposed to participate in the regulation of body fluid balance.…”

Effect of reproductive status on plasma oxytocin concentrations and the renal response to oxytocin in the conscious rat

“…The present studies suggest that the altered responsiveness does not result from changes in GFR, but observations were performed on a limited number of animals. It has, however, been reported that in the male rat doses of oxytocin which do not affect GRF are nevertheless natriuretic (Conrad et al 1986;Forsling et al 1994). Oxytocin binding sites have been identified in the inner medullary collecting duct (Stoeckel et al 1987) and evidence has been provided for an inhibitory effect of oxytocin on sodium transport across the luminal membrane of rabbit cortical collecting duct segments perfused in vitro (Inoue et al 1993).…”