Adult Female Holtzman Rats Research Articles

Maternal high-fat diet changes breathing pattern and causes excessive sympathetic discharge in juvenile offspring rat.

Early life over-nutrition, as experienced in maternal obesity, is a risk factor for developing cardiorespiratory and metabolic diseases. Here we investigated the effects of high-fat diet (HFD) consumption on the breathing pattern and sympathetic discharge to blood vessels in juvenile offspring from dams fed with HFD (O-HFD). Adult female Holtzman rats were given a standard diet (SD) or HFD from 6 wk before gestation to weaning. At weaning (P21), the male offspring from SD dams (O-SD) and O-HFD received SD until the experimental day (P28-P45). Nerve recordings performed in decerebrated in situ preparations demonstrated that O-HFD animals presented abdominal expiratory hyperactivity under resting conditions and higher vasoconstrictor sympathetic activity levels. The latter was associated with blunted respiratory-related oscillations in sympathetic activity, especially in control animals. When exposed to elevated hypercapnia or hypoxia levels, the O-HFD animals mounted similar ventilatory and respiratory motor responses as the control animals. Hypercapnia and hypoxia exposure also increased sympathetic activity in both groups but did not reinstate the respiratory-sympathetic coupling in the O-HFD rats. In freely behaving conditions, O-HFD animals exhibited higher resting pulmonary ventilation and larger variability of arterial pressure levels than the O-SD animals due to augmented sympathetic modulation of blood vessel diameter. Maternal obesity modified the functioning of cardiorespiratory systems in offspring at a young age, inducing active expiration and sympathetic overactivity under resting conditions. These observations represent new evidence about pregnancy-related complications that lead to the development of respiratory distress and hypertension in children of obese mothers.NEW & NOTEWORTHY Maternal obesity is a risk factor for developing cardiorespiratory and metabolic diseases. This study highlights the changes on the breathing pattern and sympathetic discharge to blood vessels in juvenile offspring from dams fed with HFD. Maternal obesity modified the functioning of cardiorespiratory systems in offspring, inducing active expiration and sympathetic overactivity. These observations represent new evidence about pregnancy-related complications that lead to the development of respiratory distress and hypertension in children of obese mothers.

RESPIRATORY CHANGES IN OFFSPRING OF HIGH FAT DIET FED DAMS

Several studies have demonstrated that early life over‐nutrition, such as maternal obesity, is associated with increased risk of cardio‐metabolic diseases. In the present study respiratory changes were investigated in offspring of high fat diet (HFD) fed dams. Adult female Holtzman rats (250 g) were fed with standard diet (SD) or HFD during 6 weeks before, during gestation and lactation. After weaning, male offspring of SD dams (O‐SD, n = 7–12) or HFD dams (O‐HFD, n = 7–12) were fed with SD. The results showed that O‐HFD (P28–32) presented an increase in retroperitoneal adipose tissue (0.15 ± 0.01, vs O‐SD: 0.08 ± 0.01 g/100 g of bw, p < 0.05), a higher plasma triglycerides levels (141 ± 11, vs. O‐SD 49 ± 10 mg/dl, p < 0.05) and insulin intolerance (1.28 ± 0.30, vs O‐SD: 2.25 ± 0.15 % of glucose disappearance/min, p <0.05). At P40, baseline ventilation was higher in the O‐HFD group (1.200 ± 48, vs O‐SD: 924 ± 58, ml.kg‐1.min‐1, p <0.05) due to an increase in tidal volume (9.12 ± 0.29, vs O‐SD: 7.43 ± 0.47, ml.kg‐1, p <0.05). An increased response to hypoxia was also observed in O‐HFD (1.634 ± 80, vs O‐SD: 1.325 ± 50 mL.kg‐1.min‐1, p <0.05). The results demonstrated that young offspring of obese dams have metabolic dysfunctions. The data also demonstrated that these offspring have baseline ventilatory changes as well as an exaggerated response to peripheral chemoreflex activation.Support or Funding InformationFAPESP (2015/234677), CNPq (425586/2016‐2).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

OFFSPRING OF OBESE DAMS PRESENT CHANGES IN RESPIRATORY AND SYMPATHETIC ACTIVITIES

Obesity in dams is associated with the development of several pathologies in the offspring, including cardiovascular and hormonal dysfunctions. In this study, we investigated the pattern of respiratory and sympathetic activities in the offspring of dams treated with a high‐fat diet (HFD − 45% fat). Adult female Holtzman rats (250 g) were fed with standard diet (SD) or HFD during 6 weeks before, during gestation and lactation. After weaning, male offspring of SD dams (O‐SD) or HFD dams (O‐HFD) were fed with SD. At P28–32, O‐SD and O‐HFD rats were surgically prepared to obtain the arterially‐perfused in situ preparation to examine the thoracic sympathetic, phrenic, hypoglossal and abdominal activities under basal conditions and during peripheral chemoreceptors activation (KCN −0.05%). O‐HFD rats exhibited augmented baseline phrenic inspiratory (0.80 ± 0.04 vs O‐SD: 0.57 ± 0.07 s; n=6; p < 0.05) and hypoglossal pre‐inspiratory times (0.60 ± 0.11 vs O‐SD: 0.27 ± 0.08 s, n=4; p < 0.05) compared to O‐SD. Additional expiratory bursts were observed in baseline abdominal activity of O‐HFD group, indicating the presence of active expiration (8.5 ± 2.5 vs O‐SD: 1.3 ± 0.6 events/min, n = 4 p < 0.05). Moreover, O‐HF rats showed weakened baseline respiratory‐related modulation of sympathetic activity compared to O‐HFD group. In response to stimulation of peripheral chemoreceptors, O‐HFD group showed greater abdominal reflex responses (212 ± 20 vs O‐SD: 134 ± 21 %; n = 4; p<0.05), but no significant differences were noted in the others recorded nerves comparing to O‐SD. The results indicate that male offspring of HFD‐fed dams exhibit changes in baseline respiratory pattern associated with the presence of active expiration, and blunted respiratory‐sympathetic coupling. Part of these changes persist during peripheral chemoreceptor stimulation.Support or Funding InformationFAPESP (2016/23513‐1; 2013/17251‐6) and CNPq (425586/2016‐2).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Detailed analysis of estrous-related changes in wheel running and self-stimulation

Previous studies have demonstrated that a number of behaviors change their probability of occurrence during the estrous cycle. Wheel running is known to show estrous-related changes while reports upon intracranial reinforcement (self-stimulation, ICS) have been equivocal. The present studies examined both behvaiors to further resolve the underlying behavioral determinants of these estrous effects. Data for wheel running and intracranial self-stimulation behaviors of adult female Holtzman rats were collected nightly on a minute by minute basis across the estrous cycle. It was found that: (a) both behaviors showed significant estrous-related changes in frequency; (b) the two behaviors occurred in discontinuous episodes (bursts) during the dark phase of the diurnal cycle; and (c) of three burst parameters (number/session, average length, rate of response), number proved the best predictor of estrous-related behavioral change. Burst number may reflect an important motivational parameter underlying estrous-related changes in behavior.

Effect of independent deafferentation of each border of the medial basal hypothalamus on catecholamine content of the median eminence and on serum LH and prolactin levels in ovariectomized rats

The purpose of this work was to correlate the norepinephrine (NE) and dopamine (DA) content in the region of the median eminence (ME) with serum levels of LH and prolactin in ovariectomized rats after independent deafferentation of each one of the borders of the medial basal hypothalamus (MBH). Surgical transections of the MBH or sham operations, followed by ovariectomy, were performed in adult female Holtzman rats. The following types of transections were performed: bilateral, dorsal or rostral and caudal. One week later, the animals were decapitated, trunk blood was collected for LH and prolactin quantification by RIA and the region of the ME was dissected out for catecholamine assay. Both NE and DA were measured in each individual sample by a highly sensitive enzymatic-isotopic method. Bilateral transections of the MBH induced a significant decrease in NE in the region of the ME, without altering DA levels in the same area or LH and prolactin values. Cuts of the rostral and caudal or dorsal borders of the MBH did not modify any of the parameters evaluated. These results indicate that: (a) Most noradrenergic fibers innervating the ME enter the MBH through the lateral borders. However, some residual NE activity in the ME can be detected, suggesting other sources of noradrenergic innervation of the ME. (b) Normal levels of NE in the ME are not required for the LH post-castration rise to take place.

Effect of fetal tissue on experimental (7,12-dimethylbenz[ a]anthracene) breast cancer in rats

Treatment with small quantities of fetal tissue from randomly bred Sprague—Dawley rats can either potentiate or depress the development of DMBA-induced breast tumors in young adult female Holtzman rats. The difference between potentiation and suppression of tumors depended upon whether the fetal tissue had been killed (by freeze—thawing and homogenization), which potentiated tumor development, or whether a viable mince of fetal tissue had been used, which greatly suppressed tumor development and caused a high rate of tumor regression.

Changes in catecholamine content of the median eminence precede the pro-oestrous surges of luteinizing hormone and prolactin.

Instituto de Neurobiologia, Serrano 665, Buenos Aires, Argentina (Received 9 June 1977) Changes in the levels of catecholamines in the hypothalamus during the oestrous cycle have been reported by Donoso, Stefano & Biscardi (1966) and Stefano & Donoso (1967). Shaar & Clements (1974) found that lower concentrations of dopamine and noradrenaline than those found in the hypothalamus can inhibit the release of prolactin from the rat pituitary gland. We have studied the levels of noradrenaline and dopamine in the median eminence around the time of the spontaneous preovulatory release of hormones. Adult female Holtzman rats showing at least three consecutive 4 day cycles, were killed by decapitation at 09.30, 13.00 and 17.30 h on the days of dioestrus I and pro-oestrus. After decapitation, blood was collected into centrifuge tubes and the brains were immediately removed and frozen on solid CO2. Serum was separated by centrifugation and stored at −20 °C

Effects of oestrone and progesterone on collagen and ascorbic acid content in the endometrium and myometrium of the rat.

Department of Physiology and Cell Biology, University of Kansas, Lawrence, Kansas 66045, U.S.A. Although endometrial progestational differentiation appears to be regulated precisely by ovarian steroid hormones (Yochim & DeFeo, 1963), little evidence is available concerning the hormonal effects on uterine collagen during the preimplantation stages of progestation. The present study was undertaken to examine the effects of oestrone and progesterone on endometrial and myometrial collagen content in the rat during the oestrous cycle and early pseudopregnancy. Hydroxyproline content was used as an index of extractable collagen, and ascorbic acid was also measured, since this vitamin has been implicated in the hydroxylation of proline during collagen production (Gould, 1958). Adult female Holtzman rats (200-300 g) were caged individually in temperature (23 ± 1°C)- and light-controlled (14 hr light/24 hr) quarters. Animals were allowed unrestricted access to food and water, and vaginal smears for each rat were recorded daily for at least

Changes in hypothalamic FSH-RF and pituitary FSH during the estrous cycle of rats.

Hypothalamic FSH-RF content and pituitary FSH concentration were measured in female rats during the estrous cycle. Vaginal smears were take from adult female Holtzman rats daily and only those that showed at least 2 consecutive 4-day cycles were used. The rats were killed by guillotine at 9:00 or 11:00 AM on the days of proestrus, estrus and diestrus, or at 4:30 PM on the day of proestrus. Hypothalamic FSH-RF (assay method of Mittler and Meites) content was high during the morning of diestrus and proestrus, and low on the afternoon of proestrus and morning of estrus. A significant decline in hypothalamic FSH-RF content was observed between 11:00 AM and 4:30 PM on the day of proestrus. Similar changes were observed in pituitary FSH concentration. Ovariectomy early in the morning of proestrus at least partially prevented the PM decline in hypothalamic FSH-RF content. These results suggest that FSH as well as LH are involved in the process of ovulation, and that the CNS may have a common regulatory mechanism...

Comparative potency of several progestogenic compounds in a battery of different biological tests.

This report compares the effectiveness of various compounds with progestogenic activity in a series of tests involving the chick the rat the mouse and the rabbit. The inhibition of oviduct growth stimulation of decidual growth and the Clauberg test were used for measurement of activity of 17-alpha-hydroxyprogesterone 17-alpha-hydroxyprogesterone caproate 11 dehydroprogesterone 17-alpha-ethyl-19-nortestosterone and 17-alpha-ethinyl-19-nortestosterone. In the chick oviduct test 16-day-old female white Leghorns were treated for 7 days and sacrificed on Day 8. The entire genital tract from the infundibulum to the cloaca was included in the oviduct weight. Injection of stilbestrol alone gave a typical sigmoid dose-response curve with a sharp increase in weight from 13 mg % of body weight at .05 mg daily to 1048 mg percent at 1 mg daily. A standard dose of 1 mg a day of stilbestrol was then selected for further experiments. Progesterone produced a marked inhibition of the stilbestrol-stimulated oviduct in the chick particularly when dissolved in oil; all the compounds tested showed some inhibition ability. Adult female Holtzman rats were castrated treated with 1 mg of estrone for 4 days followed by 9 days of progesterone or one of the test compounds. The uterus was exposed on Day 5 of test-drug treatment and 1 mg of histamine dihydrochloride injected into the left horn. A marked deciduoma was apparent with .5 mg progesterone daily. The degree of deciduomatogenesis was evaluated by comparing the percentage of increase of the histamine-treated horn with the other. At .2-2 mg daily progesterone gave a good dose response curve up to 400% increase when suspended in oil. Suspension of the hormone in saline with "Tween 80" decreased activity by 50%. 11-dehydroprogesterone was twice as effective as progesterone. The other compounds gave little or no response even in large doses. In mice similar tests showed the decidual response in the mouse is a more sensitive index of progestone-like activity than in the rat. No significant activity was observed with any of the test compounds except 17-alpha-ethyl-19-norethisterone. The Clauberg test in rabbits gave similar results to previously reported work. 11-dehydroprogesterone was effective at .15 mg twice the activity of progesterone. It had only a third the activity of progesterone in the Hooker-Forbes test. Both the 17-alpha-ethyl-19-nortestosterone and the 17-alpha-ethinyl-19-nortestosterone appeared to be superior to progesterone in Clauberg and chick-oviduct tests; the ethynyl derivative was superior to the ethyl derviative in the chick test; only 11-dehydroprogesterone mirrored all the activities of progesterone and was consistently superior to the hormone.

Liver vitamin content and adrenal cortical function.

THAT extracts of the adrenal gland are capable of elevating the blood sugar level and liver glycogen stores has been known for some time (Britton and Silvette, 1932). Moreover, the ability to cause deposition of glycogen in the livers of adrenalectomized rats and mice has provided a useful basis for the assay of corticoid substances (Reinecke and Kendall, 1942; Venning, et al., 1946). In view of the importance of B-vitamins in carbohydrate metabolism, it seemed desirable to determine whether the effect of the adrenal cortex on glycogen formation in the liver is accompanied by an alteration in the vitamin content of the liver. This approach also seemed of interest in view of the reported implication of pantothenic acid in adrenal function and in cholesterol metabolism (Ralli and Dumm, 1952; Guehring et al., 1952). METHODS Adult female Holtzman rats were adrenalectomized under ether anaesthesia through a lumbar approach.