Abstract P527: Angiotensin-(1-7) Attenuates Doxorubicin-Induced Aortic Dysfunction in Male and Female Rats by Distinct Mechanisms

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Omeed Rahimi ◽  
Jay L Kirby ◽  
Jasmina Varagic ◽  
E. Ann Tallant ◽  
Patricia E Gallagher
Keyword(s):  
Cumulative Dose ◽  
Vascular Function ◽  
Aortic Diameter ◽  
Female Rats ◽  
Cardiovascular Toxicity ◽  
Sprague Dawley ◽  
Male And Female ◽  
Male And Female Rats ◽  
Males And Females

Doxorubicin (Dox), a commonly used and effective chemotherapeutic agent, often produces cumulative dose-dependent cardiovascular toxicity, resulting in long-term hypertrophy and fibrosis which can lead to heart failure. Adjunct therapies are thus needed to reduce Dox-induced cardiovascular toxicity and enhance long-term quality-of-life in cancer patients, especially in pediatric patients. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the renin-angiotensin system that improves cardiac and vascular function by reducing hypertrophy and fibrosis in various animal models. In this study, juvenile Sprague-Dawley rats (male and female, n = 8-10) were administered Dox (cumulative dose of 22 mg/kg) for 6 week, in the presence and absence of Ang-(1-7) [24 μg/kg/h]. Aortic function was measured using a Vevo 2100 small animal ultrasound system. In both males and females, Dox administration increased pulse wave velocity (PWV), a measure of arterial stiffness, and co-treatment with Ang-(1-7) attenuated the Dox-induced increase (Males - 5.6 ± 0.5, Sham; 9.7 ± 1.4, Dox; 7.8 ± 0.6 m/s, Dox/Ang-(1-7), p < 0.01; Females - 5.1 ± 0.5, Sham; 14.3 ± 1.5, Dox; 7.7 ± 1.2 m/s, Dox/Ang-(1-7), p < 0.001); Ang-(1-7) alone had no effect. Dox increased aortic thickness and decreased aortic diameter at systole in males only, which was attenuated by Ang-(1-7) (aortic thickness - 0.28 ± 0.01, Sham; 0.33 ± 0.01, Dox; 0.28 ± 0.01 mm, Dox/Ang-(1-7), p < 0.01; aortic diameter - 2.8 ± 0.6, Sham; 2.3 ± 0.1, Dox; 2.5 ± 0.1 mm, Dox/Ang-(1-7); p < 0.01). No change in aortic thickness or diameter was observed following treatment with Ang-(1-7) alone. Conversely, Dox increased fibrosis in female aorta only, measured by immunohistochemistry with Picrosirius red, which was attenuated by Ang-(1-7) (5.4 ± 0.3, Sham; 7.2 ± 0.6, Ang-(1-7); 12.8 ± 2.0, Dox; 8.0 ± 1.0%, Dox/Ang-(1-7); p < 0.001). These results demonstrate that Dox causes aortic dysfunction in both males and females, albeit through different mechanisms—an increase in aortic hypertrophy in males and aortic fibrosis in females. Ang-(1-7) attenuated both the hypertrophy and fibrosis, suggesting that treatment with the heptapeptide hormone may serve as an effective adjuvant to improve Dox-induced aortic dysfunction.

Effect of long-term undernutrition on male and female rat diaphragm contractility, fatigue, and fiber types

1994 ◽  
Vol 76 (4) ◽  
pp. 1540-1547 ◽  
Author(s):  
D. J. Prezant ◽  
B. Richner ◽  
T. K. Aldrich ◽  
D. E. Valentine ◽  
E. I. Gentry ◽  
...  
Keyword(s):  
Weight Gain ◽  
Fatigue Resistance ◽  
Female Rats ◽  
Fiber Types ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Males And Females ◽  
Diaphragm Atrophy

The effects of long-term undernutrition (10 wk) on diaphragm contractility, fatigue, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by using direct stimulation at 37 degrees C. Undernutrition allowed for continued growth in males and females but with substantial reductions in weight gain. Relative to control rats of the same sex, final weights were significantly lower in undernourished males (74 +/- 3%) than females (90 +/- 5%), but weight gain was not significantly different between undernourished males (58 +/- 5%) and females (60 +/- 3%). Only in males did undernutrition significantly reduce costal diaphragm weight (to 77 +/- 5% of control). Diaphragm forces, normalized for cross-sectional area, were not significantly different from male or female control values. Fatigue resistance indexes (fatigue/baseline force) were increased at all stimulation frequencies in undernourished males but not in undernourished females. Costal diaphragm atrophy, involving types I and II fibers, occurred in undernourished males but not in undernourished females. In conclusion, despite long-term undernutrition reducing weight gain to similar levels in males and females (relative to control), there was excellent preservation of diaphragm weight, function, and structure in females but, although diaphragm atrophy occurred, there was preserved contractility and increased fatigue resistance in males.

Gonad-gonadotrope interactions: plasma gonadotrophin levels and tumour induction in long-term castrated rats

1981 ◽  
Vol 97 (2) ◽  
pp. 181-185 ◽  
Author(s):  
Daniel M. Linkie ◽  
Jacob Furth ◽  
Diane Kourelakos
Keyword(s):  
Immunohistochemical Localization ◽  
Female Rats ◽  
Male And Female ◽  
Tumour Induction ◽  
Male And Female Rats ◽  
Specific Radioimmunoassay ◽  
Gonadotrophin Secretion ◽  
Males And Females

Abstract. The patterns of gonadotrophin secretion in intact controls and in male and female rats castrated for up to 36 months were established utilizing specific radioimmunoassay methods. Plasma LH increased 14– 16-fold and FSH rose 4–8-fold in rats of either sex in the first 30 days following gonadectomy. The subsequent 30 day interval showed an additional 76% increase of LH in both sexes and increases in FSH of 32 and 61% in males and females, respectively. These levels were maintained for an additional 34 months. The number of hypophyseal gonadotrophin containing cells, studied by immunohistochemical localization techniques, increased following gonad removal in a pattern similar to that for the circulating hormones. Development of gonadotrophin secreting tumours did not correlate with plasma gonadotrophin concentrations which suggests that the gonadotropes are uniquely resistant to tumourogenesis unlike mammotropes, thyrotropes, and corticotropes.

scholarly journals A comparative study of postpneumonectomy compensatory lung response in growing male and female rats

1992 ◽  
Vol 73 (2) ◽  
pp. 446-451 ◽  
Author(s):  
H. S. Sekhon ◽  
W. M. Thurlbeck
Keyword(s):  
Body Weight ◽  
Female Rats ◽  
Normal Lung ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Lung Weight ◽  
Male And Female ◽  
Male And Female Rats ◽  
Males And Females ◽  
Lung Response

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long- and short-term gonadectomy on the hypothalamo-hypophysial (LH-releasing hormone–LH) system in oestrogen-treated male and female rats

1986 ◽  
Vol 110 (2) ◽  
pp. 367-373 ◽  
Author(s):  
N. G. Weiland ◽  
C. A. Barraclough ◽  
K. J. Catt
Keyword(s):  
Female Rats ◽  
Short Term ◽  
Male And Female ◽  
Oestradiol Treatment ◽  
Male And Female Rats ◽  
Serum Lh ◽  
Lh Release ◽  
Males And Females ◽  
Lh Releasing Hormone

ABSTRACT Considerable differences have previously been found in the hypothalamo-hypophysial responsiveness to oestrogen, depending upon the time between gonad removal and exposure to oestrogen. In the present study a detailed analysis was made of some of the differences which may exist in pituitary LH-releasing hormone (LHRH) receptors and the amount of LH released in response to electrochemical depolarization of the medial preoptic area after 2 or 7 days of oestradiol treatment of long- and short-term gonadectomized male and female rats. The pituitary glands of long-term gonadectomized males and females secreted more LH in response to two pulse injections of LHRH than did short-term gonadectomized rats. The amount of LH released on day 2, however, was equivalent to that secreted after 7 days of oestradiol treatment. Moreover, long-term gonadectomized males and females had equivalent LHRH receptor concentrations, which were greater than those of short-term gonadectomized animals. Peak serum LH concentrations observed after preoptic stimulation were equivalent in short- and long-term castrated rats after 2 days of oestrogen exposure. Serum LH concentrations following preoptic stimulation in short-term gonadectomized males and females were significantly greater on day 7 than on day 2 of oestradiol treatment, whereas in long-term gonadectomized animals the stimulated release of LH was equivalent both in magnitude and time of peak release on both days. These studies demonstrate that the differential effects of oestradiol on LH release on day 2 (no negative feedback) compared with day 7 (both negative and positive feedback exist) are not due to differences in the ability of the pituitary gland to release LH in response to LHRH, nor in the releasable pools of hypothalamic LHRH in long-term gonadectomized rats. Rather, they seem to be due to a refractoriness in some unidentified central nervous process which regulates tonic LH release in gonadectomized rats. J. Endocr. (1986) 110, 367–373

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS:

1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson
Keyword(s):  
Ascorbic Acid ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Female Rat ◽  
Feedback Effects ◽  
Male And Female ◽  
Prostate Weight ◽  
Male And Female Rats ◽  
Males And Females ◽  
Normal Males

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Male And Female ◽  
Salix Caprea ◽  
Male And Female Rats ◽  
Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

scholarly journals EFFECTS OF NEURALTICATE DURING LONG-TERM INTRODUCTION ON BEHAVIOUR OF MALE AND FEMALE RATS IN THE «OPEN FIELD»

2019 ◽  
Vol 70 (2) ◽  
pp. 130-133
Author(s):  
L.I. Bugaeva ◽  
◽  
V.V. Bagmetova ◽  
Yu.V. Markina ◽  
A.A. Kolmakov ◽  
...  
Keyword(s):  
Open Field ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Evaluation of Some Male and Female Rats’ Reproductive Hormones Following Administration of Aspartame With or Without Vitamin C or E

2021 ◽  
Vol 45 (2) ◽  
pp. 14-20
Author(s):  
Omar H Azeez
Keyword(s):  
Vitamin C ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Control Group ◽  
Male And Female ◽  
Group 4 ◽  
Male And Female Rats ◽  
Group 3 ◽  
Group 2

Aspartame (ASP) is a sugar substitute. Its use rose because it has been demonstrated to have deleterious effects after being metabolized. In the presence of antioxidant vitamins C or E, the effects of ASP on reproductive hormones of adult male and female Albino Wister rats were investigated. A total of eighty male and female rats were used in this study. The rats were divided into four groups: group 1, received no treatment; group 2, received ASP at 40 mg/kg BW; group 3, received ASP at 40 mg/kg BW with vitamin C at 150 mg/kg BW; and group 4, received ASP at 40 mg/kg BW and vitamin E at 100 mg/kg BW. All treatments were given orally by gavage needle once daily for consecutive 90 days. The levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone hormone (TH) were measured after 90 days in blood plasma. In comparison with the control group, ASP treatment resulted in lower levels of E2, FSH, and LH in male and female rats. When the antioxidants vitamin C or E was given, the effects of ASP were reversed, and the levels of E2, LH, and FSH were increased. The testosterone hormone was likewise significantly increased by ASP, but testosterone hormone concentrations were decreased by vitamin C or E treatments. Long-term ASP consumption caused interfering with testicular and ovarian hormonal activity, while vitamins C and E on the other hand, overcome longstanding consumption ASP's effects.

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