Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA234

Poster Communications

Early oxytocin inhibition of salt intake after furosemide treatment in rats?

S. L. Core2, K. Curtis1

1. Pharmacology & Physiology, Oklahoma State University Center for Health Sciences, Ochelata, Oklahoma, United States. 2. Pharmacology & Physiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, United States.


Extracellular fluid depletion and body sodium loss produce neural and behavioral responses to restore body fluid homeostasis, and these responses are influenced by sex hormones. Furosemide, a natriuretic-diuretic, increases urine flow and urinary sodium loss within an hour after treatment, but an 18-24 hour delay typically transpires before rats consume sodium solutions. In other methods of producing hypovolemia and hyponatremia, sodium ingestion is delayed in association with increased oxytocin (OT), suggesting an inhibitory role for OT in sodium intake. We hypothesized that acute furosemide-induced sodium loss and/or the associated volume loss produces central activation in centrally-projecting OT neurons that provides an initial inhibition of sodium intake. Accordingly, we examined early activation in OT neurons after furosemide using fos immunolabeling, a marker for neural activation, and assessed whether activation depends upon the presence of estrogen. Adult female Sprague Dawley rats were OVX under pentobarbital anesthesia (Pbt; 50mg/kg bw, i.p.), treated with Meloxicam (1.5mg/kg bw) for postoperative pain management, and allowed 7 days to recover; then given estradiol benzoate (EB; 10 μg/0.1 ml sesame oil, s.c.) or sesame oil vehicle (OIL; 0.1 ml, s.c.). Rats were given two s.c injections 1-hour apart of 0.15 M NaCl (ISO; 1.0 mL/kg bw; ns = 4 OIL, 5 EB) or furosemide (5 mg/kg bw; ns = 8 OIL, 8 EB); injections were separated by 1 hour. One hour after the 2nd injection, rats were anesthetized with Pbt and perfused with paraformaldehyde. Brains were removed, cut in 40 μ sections prior to immunolabeling for fos (Santa Cruz; 1:30,000) and OT (Chemicon; 1:25,000). After furosemide, fos immunoreactivity (fos-IR) was prominent in the hypothalamic supraoptic nucleus (SON) but was not different between EB- (42.4 ± 9.8) and OIL- (53.1 ± 15.2) treated rats. Fos-IR also was present in parvocellular cells of the paraventricular nucleus (PVN) after furosemide, and again, was not different between EB- (40.3 ± 8.6) and OIL- (57.6 ± 13.5) treated rats. Virtually no fos-IR neurons in the parvocellular groups of PVN were also immunolabeled for OT. Thus, acute sodium/volume loss produces selective neural activation that is not influenced by estrogen, and the early inhibition of sodium intake after furosemide does not appear to require activation of centrally-projecting OT neurons. All procedures were approved by the Oklahoma State University Center for Health Sciences Animal Care and Use Committee. Supported by OCAST HR12-196.

Where applicable, experiments conform with Society ethical requirements