The present studies investigated the influence of presystemic signals on the control of thirst, salt appetite, and vasopressin (VP) secretion in rats during nonhypotensive hypovolemia. Rats were injected with 30% polyethylene glycol (PEG) solution, deprived of food and water overnight, and then allowed to drink water, 0.15 M NaCl, or 0.30 M NaCl. The PEG treatment, which produced 30-40% plasma volume deficits, elicited rapid intakes in an initial bout of drinking, but rats consumed much more 0.15 M NaCl than water or 0.30 M NaCl. In considering why drinking stopped sooner when water or concentrated saline was ingested, it seemed relevant that little or no change in systemic plasma Na(+) concentration was observed during the initial bouts and that the partial repair of hypovolemia was comparable, regardless of which fluid was consumed. In rats that drank 0.15 M NaCl, gastric emptying was fastest and the combined volume of ingested fluid in the stomach and small intestine was largest. These and other observations are consistent with the hypothesis that fluid ingestion by hypovolemic rats is inhibited by distension of the stomach and proximal small intestine and that movement of dilute or concentrated fluid into the small intestine provides another presystemic signal that inhibits thirst or salt appetite, respectively. On the other hand, an early effect of water or saline consumption on VP secretion in PEG-treated rats was not observed, in contrast to recent findings in dehydrated rats. Thus the controls of fluid ingestion and VP secretion are similar but not identical during hypovolemia.
Although increasing research focuses on the phenomenon of body weight gain in women after menopause, the complexity of body weight regulation and the array of models used to investigate it has proven to be challenging. Here, we used ovariectomized (OVX) rats, which rapidly gain weight, to determine if receptors for ghrelin, insulin, or leptin in the dorsal vagal complex (DVC), arcuate nucleus (ARC), or paraventricular nucleus (PVN) change during post-ovariectomy weight gain. Female Sprague-Dawley rats with ad libitum access to standard laboratory chow were bilaterally OVX or sham OVX. Subgroups were weighed and then terminated on day 5, 33, or 54 post-operatively; blood and brains were collected. ELISA kits were used to measure receptors for ghrelin, insulin, and leptin in the DVC, ARC, and PVN, as well as plasma ghrelin, insulin, and leptin. As expected, body weight increased rapidly after ovariectomy. However, ghrelin receptors did not change in any of the areas for either group, nor did circulating ghrelin. Thus, the receptor:hormone ratio indicated comparable ghrelin signaling in these CNS areas for both groups. Insulin receptors in the DVC and PVN decreased in the OVX group over time, increased in the PVN of the Sham group, and were unchanged in the ARC. These changes were accompanied by elevated circulating insulin in the OVX group. Thus, the receptor:hormone ratio indicated reduced insulin signaling in the DVC and PVN of OVX rats. Leptin receptors were unchanged in the DVC and ARC, but increased over time in the PVN of the Sham group. These changes were accompanied by elevated circulating leptin in both groups that was more pronounced in the OVX group. Thus, the receptor:hormone ratio indicated reduced leptin signaling in the DVC and PVN of both groups, but only in the OVX group for the ARC. Together, these data suggest that weight gain that occurs after removal of ovarian hormones by ovariectomy is associated with selective changes in metabolic hormone signaling in the CNS. While these changes may reflect behavioral or physiological alterations, it remains to be determined whether they cause post-ovariectomy weight gain or result from it.
Sex steroids play key roles in regulating blood pressure but their impact on renal handling of sodium is unclear. Using real‐time qt‐RT‐PCR, we investigated effects of estrogen and testosterone on the expression of renal sodium transporters in CD‐1 mice consuming 1% and 4% salt diets. Six groups (n=4) included intact female and male mice (IF & IM), ovariectomized (O) and castrated (C) mice with a placebo pellet (OP & CP), and O & C mice with a 1.5 mg estrogen or 2.5 mg testosterone pellet, respectively (OE & CT). Mice at 3 weeks old and pellets came from Harlan, Inc. and Innovative Research of America, respectively. Three days after pellet implantation, mice consumed ad libitum 1% salt diet for ten days. Four mice in each group were killed, kidneys removed, RNA extracted from 10 mg mid‐cortical sections, 1 st ‐strand cDNA synthesized followed by qt‐RT‐PCR using Sybr‐green and custom PCR arrays designed by Qiagen with primers of the following: NCC, NKCC, NHE2 & 3, ENaC a, b, and g, and angiotension type II receptor I (AgII‐I). Surviving mice consumed 4% salt diet for the next ten days and procedures were repeated. After the 1% salt period, we measured higher expression of AgII‐I, ENaC (a, b, g), NKCC, NCC, NHE2 & 3 from IF mice compared to IM mice (p<0.01 – 0.001), and higher expression of NCC and NHE2 in OE compared to OP (p<0.05 – 0.01). After the 4% salt period, expression of AgII‐I, ENaC (a, b, g), NKCC, NCC, NHE2 & 3 was higher in IM mice compared to the IM‐1% salt diet group (p<0.05‐0.001) with no differences between the IF 1% & IF 4% groups. Results indicate putative sex differences in the renal handling of sodium which could contribute to blood pressure regulation. Research supported by Oklahoma INBRE 8P20GM103447.
