scholarly journals Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Natalia Zubieta-DeUrioste ◽  
Vincent Joseph ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Carotid Body ◽  
No Synthase ◽  
Male Rats ◽  
High Dose ◽  
No Production ◽  
Sprague Dawley ◽  
En Bloc ◽  
No Synthase Inhibitor ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

scholarly journals Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats

2009 ◽  
Vol 297 (6) ◽  
pp. F1606-F1613 ◽  
Author(s):  
Libor Kopkan ◽  
Md Abdul H. Khan ◽  
Agnieszka Lis ◽  
Mouhamed S. Awayda ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Sodium Reabsorption ◽  
No Production ◽  
Sprague Dawley ◽  
Appreciable Change ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Renal Responses

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 μg·min−1·100 g body wt−1; bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats ( n = 8), cholesterol induced reductions of 10 ± 2% in RBF [baseline (b) 7.6 ± 0.3 μg·min−1·100 g−1], 17 ± 3% in urine flow (b, 10.6 ± 0.9 μg·min−1·100 g−1), 29 ± 3% in sodium excretion (b, 0.96 ± 0.05 μmol·min−1·100 g−1) and 24 ± 2% in nitrite/nitrate excretion (b, 0.22 ± 0.01 nmol·min−1·100 g−1) without an appreciable change in GFR (b, 0.87 ± 0.03 ml·min−1·100 g−1). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 μg·min−1·100 g−1; n = 6). In rats pretreated with superoxide (O2−) scavenger tempol (50 μg·min−1·100 g−1; n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 μg·min−1·100 g−1; n = 6) but remained unchanged in amiloride-pretreated rats (0.2 μg·min−1·100 g−1; n = 5), indicating that Na+/K+/2Cl− cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na+/K+/2Cl− cotransporter.

Abstract 93: Hypertension and Renal Injury Induced by Nitric Oxide Depletion are Ameliorated by Concomitant Depletion of Hydrogen Sulfide

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Joost O Fledderus ◽  
Johanna A Dijk ◽  
Chantal Tilburgs ◽  
Marianne C Verhaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Renal Injury ◽  
Renal Damage ◽  
No Synthase ◽  
Tubular Epithelium ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Synthase Inhibitor

Chronic nitric oxide (NO) depletion induces hypertension and renal damage. Chronic kidney disease is associated with decreased NO availability and less renal H 2 S production. We hypothesized that combined depletion of NO and H 2 S aggravates hypertension and renal injury. Male 8-wk old Sprague Dawley rats were treated with vehicle, NO synthase inhibitor L-NG-nitroarginine (LNNA; 125 mg/L in drinking water), cystathionine-γ-lyase (CSE) inhibitor propargylglycine (PAG; 37.5 mg/kg BW ip daily) or LNNA + PAG for 1 and 4 weeks (6 rats/group). LNNA after 4w increased systolic blood pressure (SBP; 223±10 vs . 137±3 mmHg in controls; P<0.01), proteinuria (144±35 vs. 17±2 mg/d; P<0.01), uremia (16.6±4.2 vs . 7.0±0.4 mmol/L; P<0.05) and tubulo-interstitial injury (P<0.01). LNNA reduced urinary NO metabolite (NOx) excretion by ∼85% after 1w and 4w. PAG alone had no effect on SBP, renal function or injury, but did reduce urinary NOx excretion. Co-treatment with PAG ameliorated LNNA-induced hypertension (182±10 mmHg; P<0.01) and prevented proteinuria (27±3 mg/d), uremia (8.3±0.4 mmol/L) and tubulo-interstitial injury, but did not further reduce urinary NOx excretion. Renal H 2 S production was almost absent in all PAG groups after 1w and 4w (P<0.01) and was reduced in LNNA-treated rats after 4w (4.6±1.4 vs . 9.2±0.5 μmol/hr/mg; P<0.01). Renal HO-1 gene expression was strongly induced in all PAG-treated groups after 1w and 4w (4 to 19-fold; P<0.01) whereas LNNA only increased HO-1 gene expression at 4w (P<0.01). Immunohistochemistry showed that renal HO-1 protein was primarily interstitial in all PAG-treated groups at 1w and 4w. In contrast, LNNA only showed HO-1 in tubular epithelium in conjunction with protein casts. Depleting NO caused hypertension and renal damage followed by reduced renal H 2 S production and increased renal HO-1 expression. Surprisingly, concomitant inhibition of CSE ameliorated hypertension and prevented renal injury. PAG almost completely blocked renal H 2 S production and caused strong induction of renal HO-1, independently of injury, suggesting that H 2 S suppresses renal HO-1 expression. In conclusion, concomitant upregulation of HO-1 expression by inhibition of H 2 S production, prevents LNNA-induced hypertension and renal injury.

17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Control Level ◽  
No Synthase ◽  
Sprague Dawley ◽  
Response Curves ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Synthase Inhibitor

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

scholarly journals Toxicological Features ofCatha edulis(Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abdulsamad Alsalahi ◽  
Mahmood Ameen Abdulla ◽  
Mohammed Al-Mamary ◽  
Mohamed Ibrahim Noordin ◽  
Siddig Ibrahim Abdelwahab ◽  
...  
Keyword(s):  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Catha Edulis ◽  
Male And Female ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
Serum Aspartate Aminotransferase ◽  
Liver And Kidney ◽  
Kg Medium

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

Repeated-Dose and Subchronic Toxicity Studies of 2,2,2-Trichloroethanol in Sprague-Dawley Rats

1991 ◽  
Vol 10 (2) ◽  
pp. 223-232
Author(s):  
J. Peter Bercz ◽  
Merrel Robinson ◽  
Lucille M. Garner ◽  
Norbert P. Page ◽  
Greg R. Olson
Keyword(s):  
Toxic Effect ◽  
Clinical Symptoms ◽  
Clinical Chemistry ◽  
Lactic Dehydrogenase ◽  
Target Organ ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Levels

Male and female Sprague-Dawley rats were administered 2,2,2-trichloroethanol (TCE) by gavage for 14 or 90 consecutive days. The gavage solution consisted of TCE dissolved in distilled water, containing 10% Emulphor. Doses of 37.5, 75, 150, and 300 mg/kg/day in the 14-day study and 40, 80, 160, and 320 mg/kg/day for the 90-day study were employed. Evaluation of clinical symptoms, clinical chemistry, and pathology examinations did not reveal a specific toxic effect or identify a target organ. In male rats an increase of red blood cells (RBCs) and hematocrit (Hct) in both 14- and 90-day studies, as well as increased hemoglobin (Hgb) in the 90-day study was observed at the highest dose level. In the high-dose females only increase of Hgb was seen in the 14-day study. These hematopoietic indices were not accompanied by commensurate changes in reticulocytes, mean corpuscular volumes or spleen weights. Serum lactic dehydrogenase (LDH) levels were increased in males at the two highest dose levels of both studies. Other changes in chemistries were sporadic in nature and did not appear to be dose related. Collectively, there was no basis to identify a target organ. The RBC and LDH levels did not correlate with other biochemical or pathology results and did not support the hypothesis that they represent a specific toxic effect. Based on the lack of detectable toxicity of TCE at the highest doses tested in rats, the following lowest observed adverse effect levels (LOAEL) were assigned for this chemical: in the 14-day exposure, 300 mg/kg/day for both sexes; in the 90-day protocol, 320 mg/kg/day for female; and 160 mg/kg/day for male rats.

Peculiarities of influence of NO-synthase inhibitors on behavioral parameters of rats

2020 ◽  
Vol 28 (3) ◽  
pp. 275-282
Author(s):  
Valentina G. Bashkatova ◽  
Natalia G. Bogdanova ◽  
Elena V. Alexeeva ◽  
Galina A. Nazarova ◽  
Sergey K. Sudakov
Keyword(s):  
Nitric Oxide ◽  
Locomotor Activity ◽  
Motor Activity ◽  
Pain Sensitivity ◽  
Selective Inhibitor ◽  
No Synthase ◽  
Anxiety Level ◽  
Male Rats ◽  
No Synthase Inhibitor ◽  
Synthase Inhibitor

Aim. A comparative study of the influence of nitric oxide synthase (NO-synthase) inhibitors on the parameters of anxiety, motor activity and pain sensitivity of rats. Materials and Methods. The work was conducted on male rats of Wistar line. The anxiety level and locomotor activity of rats were studied in the elevated plus maze (EPM) test. Pain sensitivity of the animals was tested on the hotplate apparatus. In the work, selective inhibitor of inducible isoform of NO-synthase aminoguanidine at a dose of 50 mg/kg, and non-selective inhibitor of this enzyme N-nitro-L-arginine at a dose of 50 mg/kg, were used. Rats of the control group were introduced the equivalent quantity of normal saline. NO-synthase inducible inhibitor aminoguadinine did not produce any influence on the anxiety level, but led to reduction of the horizontal motor activity of rats. Introduction of non-selective NO-synthase inhibitor N-nitro-L-arginine was accompanied by reduction of the anxiety and of the locomotor activity of animals in the EPM test. Both investigated NO-synthase inhibitors induced alteration of pain sensitivity of rats in the form of hypoalgesia. Here, the most pronounced nociceptive effect was observed with introduction of non-selective NO-synthase inhibitor. Conclusion. In the work the evidence of participation of inducible isoform of NO-synthase in realization of the motor activity and pain sensitivity processes in rats is shown. In result of the conducted experiments it was found that introduction of non-selective NO-synthase inhibitor N-nitro-L-arginine was accompanied by evident alterations of anxious behavior, locomotor activity and nociceptive sensitivity of rats. The results obtained confirm the important role of the system of regulation of nitric oxide synthesis in neurochemical mechanisms of behavioral reactions in rats.

A Subchronic Toxicity Study of Phosflex 51B in Sprague-Dawley Rats

2001 ◽  
Vol 20 (5) ◽  
pp. 269-274 ◽  
Author(s):  
Ralph I. Freudenthal ◽  
David Brandwene ◽  
Welmoed Clous
Keyword(s):  
Food Consumption ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Significant Treatment ◽  
Sprague Dawley Rats ◽  
The Mean ◽  
Microscopic Pathology

Phosflex 51B is a flame retardant plasticizer that is blended with polyvinyl chloride films to effectively control product flammability. Its composition places it in the butylated triphenyl phosphate category. Previous studies have shown Phosflex 51B to have low acute toxicity, to lack teratogenic and mutagenic activity, and to not induce delayed peripheral neuropathy. The present study was conducted to determine the toxicity of Phosflex 51B after repeated dietary exposure. Four groups, each consisting of 20 male and 20 female Sprague-Dawley rats, received rodent diet containing either 0, 100, 400, or 1600 ppm for 90 days. Parameters measured include body weight, food consumption, clinical observations, hematology, clinical chemistry, and cholinesterase activity. Tissues were examined at necropsy for gross changes and were processed for microscopic pathology. There were no significant treatment-related effects on body weights, food consumption, hematology and clinical chemistry, or cholinesterase values. A significant increase was observed in the absolute and relative mean weights of livers in high-dose male rats, the mean relative fiver weights of the high-dose female animals, the mean relative kidney weights of the high-dose male rats, and the mean absolute weights of the adrenal glands from high-dose female rats. Neither gross nor microscopic pathology examinations revealed tissue changes in these organs or in any other organs. Although increases in fiver, kidney, and adrenal weights were observed in certain animals in the 1600-ppm high-dose group, the administration of Phosflex 51B did not result in significant treatment-related adverse effects at dietary dose levels of 100 and 400 ppm. The no-observable-effect level (NOEL) in this study is 400 ppm.

scholarly journals l-Arginine supplementation abolishes the blood pressure and endothelin response to chronic increases in plasma sFlt-1 in pregnant rats

2012 ◽  
Vol 302 (2) ◽  
pp. R259-R263 ◽  
Author(s):  
Sydney R. Murphy ◽  
Babbette LaMarca ◽  
Kathy Cockrell ◽  
Marietta Arany ◽  
Joey P. Granger
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Blood Pressure Response ◽  
No Synthase ◽  
Pressure Response ◽  
No Production ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Synthase Inhibitor

While soluble fms-like tyrosine kinase-1 (sFlt-1) and endothelin-1 (ET-1) have been implicated in the pathogenesis of preeclampsia (PE), the mechanisms whereby increased sFlt-1 leads to enhanced ET-1 production and hypertension remain unclear. It is well documented that nitric oxide (NO) production is reduced in PE; however, whether a reduction in NO synthesis plays a role in increasing ET-1 and blood pressure in response to chronic increases in plasma sFlt-1 remains unclear. The purpose of this study was to determine the role of reduced NO synthesis in the increase in blood pressure and ET-1 in response to sFlt-1 in pregnant rats. sFlt-1 was infused into normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg−1·day−1 for 6 days beginning on day 13 of gestation) treated with the NO synthase inhibitor NG-nitro-l-arginine methyl ester (100 mg/l for 4 days) or supplemented with 2% l-Arg (in drinking water for 6 days beginning on day 15 of gestation). Infusion of sFlt-1 into NP rats significantly elevated mean arterial pressure compared with control NP rats: 116 ± 2 vs. 103 ± 1 mmHg ( P < 0.05). NO synthase inhibition had no effect on the blood pressure response in sFlt-1 hypertensive pregnant rats (121 ± 3 vs. 116 ± 2 mmHg), while it significantly increased mean arterial pressure in NP rats (128 ± 4 mmHg, P < 0.05). In addition, NO production was reduced ∼70% in isolated glomeruli from sFlt-1 hypertensive pregnant rats compared with NP rats ( P < 0.05). Furthermore, prepro-ET-1 in the renal cortex was increased ∼3.5-fold in sFlt-1 hypertensive pregnant rats compared with NP rats. Supplementation with l-Arg decreased the sFlt-1 hypertension (109 ± 3 mmHg, P < 0.05) but had no effect on the blood pressure response in NP rats (109 ± 3 mmHg) and abolished the enhanced sFlt-1-induced renal cortical prepro-ET expression. In conclusion, a reduction in NO synthesis may play an important role in the enhanced ET-1 production in response to sFlt-1 hypertension in pregnant rats.

A Subchronic Toxicity Study of Fyrol PCF in Sprague-Dawley Rats

1999 ◽  
Vol 18 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Ralph I. Freudenthal ◽  
Richard T. Henrich
Keyword(s):  
Cholinesterase Activity ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Brain Cholinesterase ◽  
Sprague Dawley Rats

Fyrol PCF is a flame retardant chemical widely used to control the flam mability of rigid polyurethane foams and polyester foam systems. It has moderate acute toxicity and was shown to lack mu-tagenic activity. The present study was conducted to determine the toxicity of Fyrol PCF after repeated dietary exposure. Five groups, each consisting of 20 male and 20 female Sprague-Dawley rats, a diet containing either 0, 800, 2500, 7500, or 20,000 ppm Fyrol PCF for 90 days. Data collected include clinical observations, food consumption, body weights, organ weights, urinalysis, hematology, clinical chemistry, brain cholinesterase activity, and gross and microscopic pathology. The mean body weight of animals receiving 20,000 ppm was significantly lower than control values for most study weeks. No clinical signs were noted during cage-side observations. Liver weights were increased in male rats in all treatment groups, and in female rats in both the mid-and high-dose groups. No treatment-related histopathologic changes were observed in the livers of animals that 800, 2500, or 7500 ppm Fyrol PCF; however very mild periportal hepato-cellular swelling was seen in certain of the 20,000 ppm animals. Mean kidney weights were significantly greater in the male animals given 2500, 7500, and 20,000 ppm. Very mild cortical tubular degenerative changes were found in kidneys of male rats that 7500 ppm or 20,000 ppm and in female animals that ingested 20,000 ppm Fyrol PCF. An increase in the incidence of very mild thyroid follicular changes was found in the two highest dose groups. Fyrol PCF did not affect hematology or clinical chemistry parameters, nor did it significantly inhibit brain cholinesterase activity. None of the observed minimal treatment-related changes appear to have human relevance, because they occurred only at the highest doses used in the study. The no observable effect level in this study is 2500 ppm. Fyrol PCF demonstrated low subchronic toxicity in this study.

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