scholarly journals Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats

2020 ◽  
Vol 318 (2) ◽  
pp. R418-R427 ◽  
Author(s):  
Reham H. Soliman ◽  
Jermaine G. Johnston ◽  
Eman Y. Gohar ◽  
Crystal M. Taylor ◽  
David M. Pollock

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.

2009 ◽  
Vol 87 (6) ◽  
pp. 460-470 ◽  
Author(s):  
Claude Lajoie ◽  
Viviane El-Helou ◽  
Cindy Proulx ◽  
Robert Clément ◽  
Hugues Gosselin ◽  
...  

Rapamycin represents a recognized drug-based therapeutic approach to treat cardiovascular disease. However, at least in the female heart, rapamycin may suppress the recruitment of putative signalling events conferring cardioprotection. The present study tested the hypothesis that rapamycin-sensitive signalling events contributed to the cardioprotective phenotype of the female rat heart after an ischemic insult. Rapamycin (1.5 mg/kg) was administered to adult female Sprague–Dawley rats 24 h after complete coronary artery ligation and continued for 6 days. Rapamycin abrogated p70S6K phosphorylation in the left ventricle of sham rats and the noninfarcted left ventricle (NILV) of 1-week postmyocardial-infarcted (MI) rats. Scar weight (MI 0.028 ± 0.006, MI+rapamycin 0.064 ± 0.004 g) and surface area (MI 0.37 ± 0.08, MI+rapamycin 0.74 ± 0.03 cm2) were significantly larger in rapamycin-treated post-MI rats. In the NILV of post-MI female rats, rapamycin inhibited the upregulation of eNOS. Furthermore, the increased expression of collagen and TGF-β3 mRNAs in the NILV were attenuated in rapamycin-treated post-MI rats, whereas scar healing was unaffected. The present study has demonstrated that rapamycin-sensitive signalling events were implicated in scar formation and reactive fibrosis. Rapamycin-mediated suppression of eNOS and TGF-β3 mRNA in post-MI female rats may have directly contributed to the larger infarct and attenuation of the reactive fibrotic response, respectively.


1998 ◽  
Vol 32 (4) ◽  
pp. 477-482 ◽  
Author(s):  
Maud Palm

Chronic progressive nephrosis (CPN) in rats may not only become a problem in long-term toxicity studies but also in short-term studies, if the breeding stock is not carefully selected with respect to the kidney function. This paper presents differences in kidney function between young rats of the same strain, Sprague-Dawley, but from two different breeders ('set A' and 'set B' rats). In set A rats, protein in the urine was present in the males, which is a common finding. In set B rats, not only the males but also the females excreted protein in the urine. The method used to detect protein in the urine does not normally show a positive protein result in the young female rats. At the age of 3 months signs of chronic progressive nephrosis were observed in 55% of the males and in 15% of the females in set B. Two months later, the incidence had increased to about 70–80% in males and 50% in females. At 8 months, the incidence was similar, but the severity had increased. These values were compared with those obtained from the set A rats, none of which showed any signs of the disease at the age of 5 months and only 5% of the males and females at the age of 8 months. The results indicated that an increased excretion of protein in the urine may be used as an indicator for chronic progressive nephrosis in the rat and that not only the strain but also the source is important in selecting laboratory rats for toxicity studies.


2004 ◽  
Vol 287 (1) ◽  
pp. H165-H171 ◽  
Author(s):  
Yi Xu ◽  
Stephen J. Armstrong ◽  
Ivan A. Arenas ◽  
Daniel J. Pehowich ◽  
Sandra T. Davidge

Aging and estrogen deficiency increase the risk for developing cardiovascular disease (CVD). Oxidative stress has also been implicated in the pathophysiology of CVD and in ischemia-reperfusion (I/R) injury. We tested the hypothesis that chronic in vivo estrogen treatment or superoxide inhibition with the SOD mimetic EUK-8 improves cardiac functional recovery after I/R in the aged female rat. Sprague-Dawley rats (12–14 mo) were used as follows: intact ( n = 6), ovariectomized + placebo (OVX, n = 6), OVX + EUK-8 (EUK-8, 3 mg/kg, n = 6), and OVX + estrogen (1.5 mg/pellet, 60 days release, n = 6). Perfused isolated hearts were subjected to global ischemia (25 min) followed by reperfusion (40 min). Functional recovery after I/R and myocardial protein expression of NADPH oxidase (p22, p67, and gp91 phox), inducible nitric oxide synthase (NOS), endothelial NOS, and SOD1, as well as nitrotyrosine levels (as a marker for peroxynitrite), were assessed. Compared with OVX, EUK-8 and estrogen markedly improved functional recovery after I/R, which was associated with a decrease in NADPH oxidase expression and nitrotyrosine staining. However, estrogen increased inducible NOS expression, whereas EUK-8 had little effect. There were no significant changes in endothelial NOS and SOD1 expression among the groups. These results indicate that EUK-8 and estrogen improved cardiac recovery after I/R. Given the controversy surrounding hormone replacement therapy, EUK-8 may be an alternative to estrogen in protecting those at risk for myocardial ischemia in the aging population.


2021 ◽  
Vol 09 ◽  
Author(s):  
Asra Parveen ◽  
Vijay kumar B. Malashetty ◽  
Sushruta Marla ◽  
Shanth Reddy ◽  
Sidramappa Sirsand ◽  
...  

Background: Silver nanoparticles have been widely used in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. Objectives: The purpose of this study was to investigate the safety of silver nanoparticles by determining its potential toxicity following 28 days administration in Sprague Dawley rats. Method: The silver nanoparticles were administered by intravenous injection at the doses of 100, 200 and 500 µg/kg body weight for 28 consecutive days. Animals in the control group were received sterile water for injection. Each group consists of 10 male and 10 female rats. Results: No treatment related effects were seen in any of the parameters monitored in rats given 100, 200 and 500 µg/kg body weight/day of silver nanoparticles. Conclusion: The study proved that the use of up to 500 µg/kg body weight biosynthesized silver nanoparticles have no toxic effect in the target organs and found safe. However, the safety of the nanoparticles might be attributed to the covering of biological moieties on nanoparticles. Hence, the biofunctionalized nanoparticles can be safely used by selecting the required size and dose in medicines and drug delivery systems.


1997 ◽  
Vol 9 (4) ◽  
pp. 324-330 ◽  
Author(s):  
Alon Eliakim ◽  
Mark Y. Moromisato ◽  
David Y. Moromisato ◽  
Dan M. Cooper

In this study, the hypothesis that improvements in functional and structural measures could be detected in the young, female rat with only 5 days of moderate treadmill training was tested. Eight-week-old female Sprague-Dawley rats were divided randomly into control (n = 10) and training groups (n = 11). Over the 5-day period, running duration and treadmill speed increased progressively. Maximal running time and gas exchange were measured on Day 6. In trained compared with control rats, maximal running time was 54% greater (p < .005), right hindlimb muscle was 16% heavier (p < .01), and end-exercise respiratory exchange ratio (RER) was 17% lower (p < .05). Substantial metabolic and structural adaptations occurred in young female rats after only 5 days of treadmill training. This protocol may be useful in discovering the initiating mechanisms of the training response in the young organism.


2019 ◽  
Vol 122 (03) ◽  
pp. 252-261 ◽  
Author(s):  
Afroza Ferdouse ◽  
Shan Leng ◽  
Tanja Winter ◽  
Harold M. Aukema

AbstractOxylipins are bioactive lipid mediators synthesised from PUFA. The most well-known oxylipins are the eicosanoids derived from arachidonic acid (ARA), and many of them influence cardiac physiology in health and disease. Oxylipins are also formed from other n-3 and n-6 PUFA such as α-linolenic acid (ALA), EPA, DHA and linoleic acid (LA), but fundamental data on the heart oxylipin profile, and the effect of diet and sex on this profile, are lacking. Therefore, weanling female and male Sprague–Dawley rats were given American Institute of Nutrition (AIN)-93G-based diets modified in oil composition to provide higher levels of ALA, EPA, DHA, LA and LA + ALA, compared with control diets. After 6 weeks, free oxylipins in rat hearts were increased primarily by their precursor PUFA, except for EPA oxylipins, which were increased not only by dietary EPA but also by dietary ALA or DHA. Dietary DHA had a greater effect than ALA or EPA on reducing ARA oxylipins. An exception to the dietary n-3 PUFA-lowering effects on ARA oxylipins was observed for several ARA-derived PG metabolites that were higher in rats given EPA diets. Higher dietary LA increased LA oxylipins, but it had no effect on ARA oxylipins. Overall, heart oxylipins were higher in female rats, but this depended on dietary treatment: the female oxylipin:male oxylipin ratio was higher in rats provided the ALA compared with the DHA diet, with other diet groups having ratios in between. In conclusion, individual PUFA and sex have unique and interactive effects on the rat heart free oxylipin profile.


Author(s):  
Arnold Gutierrez ◽  
Kevin M. Creehan ◽  
Michael A. Taffe

AbstractBackgroundThe ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy. Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established.MethodWe adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.ResultsInhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups.ConclusionsThis work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ∼50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.


2018 ◽  
Vol 37 (3) ◽  
pp. 241-262 ◽  
Author(s):  
Rachel Z. Fraser ◽  
Mithila Shitut ◽  
Puja Agrawal ◽  
Odete Mendes ◽  
Sue Klapholz

The leghemoglobin protein (LegH) from soy ( Glycine max) expressed in Pichia pastoris (LegH preparation, LegH Prep) imparts a meat-like flavor profile onto plant-based food products. The safety of LegH Prep was evaluated through a series of in vitro and in vivo tests. The genotoxic potential of LegH Prep was assessed using the bacterial reverse mutation assay (Ames test) and the in vitro chromosome aberration test. LegH Prep was nonmutagenic and nonclastogenic in each test, respectively. Systemic toxicity was assessed in a 28-day dietary study in male and female Sprague Dawley rats. There were no mortalities associated with the administration of LegH Prep. There were no clinical observations, body weight, ophthalmological, clinical pathology, or histopathological changes attributable to LegH Prep administration. There were no observed effects on male reproduction in this study, but the suggestion of a potential estrous cycle distribution effect in female rats prompted a second comprehensive 28-day dietary study in female Sprague Dawley rats. This study demonstrated that female reproductive parameters were comparable between rats treated with LegH Prep and concurrent control rats. These studies establish a no observed adverse effect level of 750 mg/kg/d LegH, which is over 100 times greater than the 90th percentile estimated daily intake. Collectively, the results of the studies presented raise no issues of toxicological concern with regard to LegH Prep under the conditions tested.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Timothy J Stodola ◽  
Daniela Didier ◽  
Michael Flister ◽  
Jozef Lazar ◽  
Andrew Greene

Angiogenesis is the formation of new microvessels from existing vascular beds. AngII, a downstream product of renin, has been shown to be essential mediator of skeletal muscle angiogenesis in Dahl Salt Sensitive (SS) and Sprague Dawley rats, C57BL/6 mice, and human endothelial cells in vitro. Using partial chromosome introgression from the Brown Norway (BN) rat into the SS rat we have created two congenic lines with small (<300 Kbp) BN substitutions that differ by 23 Kbp. The congenic regions define an angiogenesis locus that contains one gene, Btg2 . Sanger sequencing revealed no sequence variants in exons of Btg2 between the BN and SS strains. Angiogenesis was measured using an in vivo electrical stimulation model of one hindlimb, with the contralateral leg acting as the control, in males and females of both new congenic strains. Males from Btg2 BN have angiogenesis (TA=20.0±4.5% increase in vessel density in stimulated leg relative to unstimulated leg, EDL=15.8±5.8%,) while Btg2 SS males did not have angiogenesis (TA=5.1±2.2%, EDL=4.4±2.7%). Females of both strains had angiogenesis: Btg2 BN (TA=15.8±4.3%, EDL=3.4%), Btg2 SS (TA=14.5±2.0%, EDL=14.6±2.5%). Stimulation significantly increased Btg2 expression in both males and females. Btg2 SS males had a significantly greater increase in Btg2 mRNA in the stimulated muscle relative to unstimulated than Btg2 BN males (5.0±0.9 versus 2.1± 0.3), but there was no difference in stimulated females (Btg2 BN 2.5±0.2, Btg2 SS 3.2±1.5). To test the hypothesis that Btg2 impacted renin expression, we cloned the renin proximal promoter into a vector to drive luciferase, and co-transfected HEK-293 cells with this and vector(s) expressing Btg2 or Hoxb9 and Btg2 . Normalized luciferase activity was 4.52±0.30 (arbitrary units) with an empty vector control and suppressed with the Btg2 vector to 1.45±0.07. Co-expression of Btg2 and Hoxb9 lead to a further reduction in luciferase activity to 0.40±0.04. These data suggest the elevated Btg2 expression observed in Btg2 SS strain may be acting to suppress renin expression through renin proximal promoter transcription factor Hoxb9 , leading to an inhibited angiogenic response.


1978 ◽  
Vol 79 (1) ◽  
pp. 133-134 ◽  
Author(s):  
M. B. TER HAAR ◽  
CATHERINE A. WILSON

*A.R.C. Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT, and ‡Department of Physiology, Royal Veterinary College, London, NW1 OTU (Received 28 March 1978) Ovulation can be induced precociously in the prepubertal female rat by the administration of pregnant mare serum gonadotrophin (PMSG), provided that the animal weighs over 60 g (Wilson, Endersby & McDonald, 1974). The hormonal changes brought about by this treatment have been studied (J. C. Buckingham, M. B. ter Haar, A. S. McNeilly & C. A. Wilson, data to be published) and it has been found that the preovulatory concentrations of radioimmunoassayable luteinizing hormone (LH) varied according to the antiserum used. These findings are described in the present communication. Female Sprague–Dawley rats (Tuck & Sons, Rayleigh, Essex) were brought into the department on day 21 of life, kept under conditions of controlled lighting (lights on 05.00–19.00 h) and provided with pelleted rat diet (No. 86, Dixon &


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