Infarct size is increased in female post-MI rats treated with rapamycin

2009 ◽  
Vol 87 (6) ◽  
pp. 460-470 ◽  
Author(s):  
Claude Lajoie ◽  
Viviane El-Helou ◽  
Cindy Proulx ◽  
Robert Clément ◽  
Hugues Gosselin ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Female Rats ◽  
Coronary Artery Ligation ◽  
Female Rat ◽  
Sprague Dawley ◽  
Ischemic Insult ◽  
Fibrotic Response ◽  
Artery Ligation ◽  
Sprague Dawley Rats ◽  
Scar Healing

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.

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
Keyword(s):  
Protein Expression ◽  
Time Of Day ◽  
Female Rats ◽  
Female Rat ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Endothelin System ◽  
Males And Females ◽  
Epithelial Sodium Channel Enac

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.

scholarly journals Functional and Muscle Size Response to 5 Days of Treadmill Training in Young Rats

1997 ◽  
Vol 9 (4) ◽  
pp. 324-330 ◽  
Author(s):  
Alon Eliakim ◽  
Mark Y. Moromisato ◽  
David Y. Moromisato ◽  
Dan M. Cooper
Keyword(s):  
Young Female ◽  
Treadmill Training ◽  
Female Rats ◽  
Muscle Size ◽  
Female Rat ◽  
Sprague Dawley ◽  
Running Time ◽  
Sprague Dawley Rats ◽  
Hindlimb Muscle ◽  
Training Response

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.

Orally administered NHE1 inhibitor cariporide reduces acute responses to coronary occlusion and reperfusion

1999 ◽  
Vol 276 (2) ◽  
pp. H749-H757 ◽  
Author(s):  
Rachael A. Humphreys ◽  
James V. Haist ◽  
Subrata Chakrabarti ◽  
Qingping Feng ◽  
J. Malcolm O. Arnold ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Left Ventricle ◽  
Mrna Expression ◽  
Interventricular Septum ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Coronary Artery Ligation ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Acute Responses ◽  
Ischemic And Reperfusion Injury

Na+/H+exchange (NHE) mediates myocardial ischemic and reperfusion injury. We examined the effects of dietary administration of the potent and selective NHE1 inhibitor cariporide on acute responses to coronary artery ligation and reperfusion in the anesthetized rat. Male Sprague-Dawley rats received control rat chow or an identical diet containing 3 parts per million of cariporide for 1 wk before 225 min of occlusion of the left main coronary artery or 45 min of occlusion followed by 180 min of reperfusion. Hearts were excised and divided into left ventricle, right ventricle, and interventricular septum for analysis of NHE1 mRNA expression and apoptosis by staining with terminal deoxynucleotidyl transferase-mediated nick end labeling. Ischemia and reperfusion were associated with a threefold elevation in NHE1 mRNA expression in control animals that was significantly reduced in cariporide-fed rats. Cariporide reduced mortality from 26% of animals to 0%. The incidence of all arrhythmias was significantly reduced, including ventricular fibrillation (from 42 to 0%) and ventricular tachycardia (from 81 to 15%), as well as the number of ventricular premature beats (from 70 ± 12 to 17 ± 6). Cariporide moderately reduced apoptosis only in the reperfused left ventricle to values not significantly greater than those in sham-operated animals, and this was associated with a significantly higher ratio of Bcl-2 to Bax. This study suggests that NHE inhibition with dietary cariporide represents an effective management of acute postinfarction responses.

scholarly journals Dietary n-6 and n-3 PUFA alter the free oxylipin profile differently in male and female rat hearts

2019 ◽  
Vol 122 (03) ◽  
pp. 252-261 ◽  
Author(s):  
Afroza Ferdouse ◽  
Shan Leng ◽  
Tanja Winter ◽  
Harold M. Aukema
Keyword(s):  
Dietary Treatment ◽  
Interactive Effects ◽  
Female Rats ◽  
Female Rat ◽  
Sprague Dawley ◽  
Oil Composition ◽  
American Institute ◽  
Sprague Dawley Rats ◽  
Rat Hearts ◽  
Health And Disease

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.

Oxidative stress contributes to vascular endothelial dysfunction in heart failure

2001 ◽  
Vol 281 (4) ◽  
pp. H1767-H1770 ◽  
Author(s):  
Julia H. Indik ◽  
Steven Goldman ◽  
Mohamed A. Gaballa
Keyword(s):  
Heart Failure ◽  
Normal Control ◽  
Coronary Artery Ligation ◽  
No Production ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Sod Activity ◽  
Sprague Dawley Rats ◽  
Peripheral Arterial

Congestive heart failure (HF) is characterized by inadequate nitric oxide (NO) production in the vasculature. Because NO is degraded by oxygen radicals, we hypothesized that NO is degraded faster in HF from inadequate peripheral arterial antioxidant reserves. HF was induced in male Sprague-Dawley rats by left coronary artery ligation. Vascular endothelial function was evaluated by measuring the NO-mediated vasorelaxation response to acetylcholine (ACh; 10−9–10−4M) in excised aortas. This was repeated with the free radical generator pyrogallol (20 μM) and again with pyrogallol and superoxide dismutase (SOD; 60 U/ml). Aortic and myocardial SOD activity was also determined. ACh-induced vasorelaxation was reduced in HF ( n = 9) compared with normal control rats ( n = 11; P < 0.001). Pyrogallol further reduced vasorelaxation in HF: 74 ± 11% at 10−4M ACh versus 58 ± 10% in normal control rats ( P < 0.004). There was a trend ( P = 0.06) toward reduced SOD activity in HF aortas. In conclusion, altered NO-dependent vasorelaxation in HF is in part due to excessive degradation of NO and is likely related to reduced vascular SOD activity.

Large- and Medium-sized Arteries Remaining in Transmural Scar Distal to Permanent Coronary Ligation Undergo Neointimal Hyperplasia and Inward Remodeling

2021 ◽  
Vol 69 (5) ◽  
pp. 321-338
Author(s):  
Eduard I. Dedkov
Keyword(s):  
Structural Integrity ◽  
Neointimal Hyperplasia ◽  
Coronary Artery Ligation ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Coronary Ligation ◽  
Extracellular Matrix Components ◽  
Vessel Integrity

This study aimed to investigate the structural integrity and dynamic changes in chronically occluded residual arteries found in post–myocardial infarction (MI) scar. A transmural MI was induced in middle-aged, male Sprague-Dawley rats by left coronary artery ligation. The rats were euthanized 3 days and 1, 2, 4, 8, and 12 weeks after MI, and their hearts were processed into paraffin for histology, immunohistochemistry, and quantitative morphometry. It has been found that large- and medium-sized arteries were able to survive inside the transmural scars for 12 post-MI weeks. Furthermore, most residual arteries preserved their structural integrity for up to 2 weeks post-MI, but gradually all disused vessels had undergone neointimal hyperplasia and inward remodeling at later time periods. In addition, the replacement of vascular smooth muscle cells in the wall of residual arteries by extracellular matrix components led to a disruption of the vessel integrity and progressive obliteration of their lumen between 4 and 12 post-MI weeks. Taken together, this study demonstrate that residual arteries in post-infarcted region were capable of maintaining their structural integrity, including the patent lumen, during two post-MI weeks, suggesting that during this period they can be used as potential conduits for conceivable reflow of arterial blood within the scarred region of the heart

Modulating the Infarcted Ventricle’s Refractoriness with an Epicardial Biomaterial

2020 ◽  
pp. jim-2020-001486 ◽  
Author(s):  
Ikeotunye Royal Chinyere ◽  
Mathew Hutchinson ◽  
Talal Moukabary ◽  
Jen Watson Koevary ◽  
Elizabeth Juneman ◽  
...  
Keyword(s):  
Dermal Fibroblasts ◽  
Monophasic Action Potential ◽  
Coronary Artery Ligation ◽  
Sprague Dawley ◽  
Electrophysiologic Study ◽  
Artery Ligation ◽  
Reduced Ejection Fraction ◽  
Sprague Dawley Rats ◽  
Increased Risk ◽  
Reentrant Circuit

Patients diagnosed with heart failure with reduced ejection fraction (HFrEF) are at increased risk of monomorphic ventricular tachycardia (VT) and ventricular fibrillation. The presence of myocardial fibrosis provides both anatomical and functional barriers that promote arrhythmias in these patients. Propagation of VT in a reentrant circuit depends on the presence of excitable myocardium and the refractoriness of the circuit. We hypothesize that myocardial refractoriness can be modulated surgically in a model of HFrEF, leading to decreased susceptibility to VT.Male Sprague-Dawley rats were infarcted via permanent left coronary artery ligation. At 3 weeks post-infarction, engineered grafts composed of human dermal fibroblasts cultured into a polyglactin-910 biomaterial were implanted onto the epicardium to cover the area of infarction. Three weeks post-graft treatment, all rats underwent a terminal electrophysiologic study to compare monophasic action potential electroanatomic maps and susceptibility to inducible monomorphic VT.HFrEF rats (n=29) demonstrated a longer (p=0.0191) ventricular effective refractory period (ERP) and a greater (p=0.0394) VT inducibility compared with sham (n=7). HFrEF rats treated with the graft (n=12) exhibited no change in capture threshold (p=0.3220), but had a longer ventricular ERP (p=0.0029) compared with HFrEF. No statistically significant change in VT incidence was found between HFrEF rats treated with the graft and untreated HFrEF rats (p=0.0834).Surgical deployment of a fibroblast-containing biomaterial in a rodent ischemic cardiomyopathy model prolonged ventricular ERP as measured by programmed electrical stimulation. This hypothesis-generating study warrants additional studies to further characterize the antiarrhythmic or proarrhythmic effects of this novel surgical therapy.

scholarly journals Angiotensin II-mediated posttranslational modification of nNOS in the PVN of rats with CHF: role for PIN

2013 ◽  
Vol 305 (6) ◽  
pp. H843-H855 ◽  
Author(s):  
Neeru M. Sharma ◽  
Tamra L. Llewellyn ◽  
Hong Zheng ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Molecular Mechanism ◽  
Neuronal Cell ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Sprague Dawley Rats ◽  
Catalytically Active

An increased sympathetic drive is an adverse characteristic in chronic heart failure (CHF). The protein expression of neuronal nitric oxide synthase (nNOS)- and hence nitric oxide (NO)-mediated sympathoinhibition is reduced in the paraventricular nucleus (PVN) of rats with CHF. However, the molecular mechanism(s) of nNOS downregulation remain(s) unclear. The aim of the study was to reveal the underlying molecular mechanism for the downregulation of nNOS in the PVN of CHF rats. Sprague-Dawley rats with CHF (6–8 wk after coronary artery ligation) demonstrated decreased nNOS dimer/monomer ratio (42%), with a concomitant increase in the expression of PIN (a protein inhibitor of nNOS known to dissociate nNOS dimers into monomers) by 47% in the PVN. Similarly, PIN expression is increased in a neuronal cell line (NG108) treated with angiotensin II (ANG II). Furthermore, there is an increased accumulation of high-molecular-weight nNOS-ubiquitin (nNOS-Ub) conjugates in the PVN of CHF rats (29%). ANG II treatment in NG108 cells in the presence of a proteasome inhibitor, lactacystin, also leads to a 69% increase in accumulation of nNOS-Ub conjugates immunoprecipitated by an antiubiquitin antibody. There is an ANG II-driven, PIN-mediated decrease in the dimeric catalytically active nNOS in the PVN, due to ubiquitin-dependent proteolytic degradation in CHF. Our results show a novel intermediary mechanism that leads to decreased levels of active nNOS in the PVN, involved in subsequent reduction in sympathoinhibition during CHF, offering a new target for the treatment of CHF and other cardiovascular diseases.

EVIDENCE FOR PLEIOMORPHISM OF LUTEINIZING HORMONE IN PERIPUBERTAL FEMALE RATS

1978 ◽  
Vol 79 (1) ◽  
pp. 133-134 ◽  
Author(s):  
M. B. TER HAAR ◽  
CATHERINE A. WILSON
Keyword(s):  
Luteinizing Hormone ◽  
Female Rats ◽  
Female Rat ◽  
Hormonal Changes ◽  
Sprague Dawley ◽  
Present Communication ◽  
Royal Veterinary College ◽  
Animal Physiology ◽  
Sprague Dawley Rats ◽  
Pregnant Mare Serum Gonadotrophin

*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 &

scholarly journals Effects of Large Doses of Androgen on Rodent Erythropoiesis and Body Composition

Blood ◽  
1965 ◽  
Vol 26 (4) ◽  
pp. 411-420 ◽  
Author(s):  
DAVID G. NATHAN ◽  
FRANK H. GARDNER ◽  
Alvera L. Kan
Keyword(s):  
Body Composition ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Red Cell ◽  
Sprague Dawley ◽  
Renal Hypertrophy ◽  
Lean Tissue ◽  
Sprague Dawley Rats ◽  
Erythropoietic Response

Abstract Six weeks treatment of male and female mature Sprague-Dawley rats with 8 mg. testosterone enanthate per week produced varied effects depending upon the sex of the animal. Compared to controls, the androgen-treated female rats exhibited a greater gain in body weight which was predominantly water. There was concomitant renal hypertrophy and fat loss. An accelerated rate of erythropoiesis produced a gain in total red cell volume out of proportion to the accretion of lean tissue. Treated male rats gained somewhat less water and lean tissue and much less fat than controls. Definite evidence of acceleration of erythropoiesis was not observed. It is concluded that the female rat is more sensitive to the erythropoietic effects of large doses of androgen than is the male. The erythropoietic response to androgen in the female rat appears to be independent of the effects of the hormone on body composition.

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