Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists

1998 ◽  
Vol 274 (4) ◽  
pp. R931-R938 ◽  
Author(s):  
Xi-Ping Ni ◽  
Robert A. Kesterson ◽  
Shubh D. Sharma ◽  
Victor J. Hruby ◽  
Roger D. Cone ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Urinary Sodium Excretion ◽  
Melanocortin Receptor ◽  
Unilateral Nephrectomy ◽  
Sprague Dawley ◽  
Receptor Antagonists ◽  
Pharmacological Characterization ◽  
Melanocyte Stimulating Hormone ◽  
Sprague Dawley Rats

γ-Melanocyte-stimulating hormone (γ-MSH), atrial natriuretic peptide (ANP), and oxytocin have been identified as candidate hormonal mediators of the reflex natriuresis that follows acute unilateral nephrectomy (AUN). Pharmacological characterization of the third melanocortin receptor (MC3-R) indicates that it uniquely responds to physiological concentrations of γ-MSH. We tested the roles of γ-MSH, ANP, and oxytocin in the postnephrectomy natriuresis by carrying out AUN during continuous intrarenal infusion of specific antagonists for their cognate receptors. In anesthetized Sprague-Dawley rats, urinary sodium excretion (UNaV) increased from 0.34 ± 0.04 to 1.12 ± 0.11 μeq/min 90 min after AUN ( P < 0.001). No change in UNaV occurred in rats undergoing a sham AUN procedure. Plasma immunoreactive γ-MSH concentration was 53 ± 8 fmol/ml after sham AUN but 112 ± 17 fmol/ml after AUN ( P < 0.01). SHU-9119 and SHU-9005 are substituted derivatives of α-MSH with potent antagonism at the MC3-R in vitro. Infusion of these compounds at 5 pmol/min completely blocked the natriuretic response to AUN despite a similar elevation in plasma γ-MSH (111 ± 12 vs. 49 ± 8 fmol/ml in sham rats, P < 0.01). Intrarenal infusion of the ANP receptor antagonist A-71915 (5 pmol/min) or the oxytocin receptor antagonist [d(CH2)5 1, Tyr(Me)2,Orn8] vasotocin (10 pmol/min) effectively inhibited the natriuresis induced by intravenous infusion of ANP or oxytocin (each at 1 pmol/min), respectively, but did not block the natriuresis after AUN. Plasma immunoreactivity of these peptides was not increased after AUN. These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma γ-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R. The data indicate that γ-MSH or a closely related peptide mediates postnephrectomy natriuresis and provide further support for the possibility that γ-MSH may play a wider role in sodium homeostasis.

scholarly journals Renal medullary ETB receptors produce diuresis and natriuresis via NOS1

2008 ◽  
Vol 294 (5) ◽  
pp. F1205-F1211 ◽  
Author(s):  
Daisuke Nakano ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Renal Medulla ◽  
Urinary Sodium Excretion ◽  
Receptor Activation ◽  
No Production ◽  
Sprague Dawley ◽  
Receptor Stimulation ◽  
Water Excretion ◽  
Sprague Dawley Rats

Endothelin-1 (ET-1) plays an important role in the regulation of salt and water excretion in the kidney. Considerable in vitro evidence suggests that the renal medullary ETB receptor mediates ET-1-induced inhibition of electrolyte reabsorption by stimulating nitric oxide (NO) production. The present study was conducted to test the hypothesis that NO synthase 1 (NOS1) and protein kinase G (PKG) mediate the diuretic and natriuretic effects of ETB receptor stimulation in vivo. Infusion of the ETB receptor agonist sarafotoxin S6c (S6c: 0.45 μg·kg−1·h−1) in the renal medulla of anesthetized, male Sprague-Dawley rats markedly increased the urine flow (UV) and urinary sodium excretion (UNaV) by 67 and 120%, respectively. This was associated with an increase in medullary cGMP content but did not affect blood pressure. In addition, S6c-induced diuretic and natriuretic responses were absent in ETB receptor-deficient rats. Coinfusion of NG-propyl-l-arginine (10 μg·kg−1·h−1), a selective NOS1 inhibitor, suppressed S6c-induced increases in UV, UNaV, and medullary cGMP concentrations. Rp-8-Br-PET-cGMPS (10 μg·kg−1·h−1) or RQIKIWFQNRRMKWKK-LRK5H-amide (18 μg·kg−1·h−1), a PKG inhibitor, also inhibited S6c-induced increases in UV and UNaV. These results demonstrate that renal medullary ETB receptor activation induces diuretic and natriuretic responses through a NOS1, cGMP, and PKG pathway.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

2013 ◽  
Vol 32 (5) ◽  
pp. 385-394 ◽  
Author(s):  
Antoinette Y. Odendaal ◽  
Narendra S. Deshmukh ◽  
Tennille K. Marx ◽  
Alexander G. Schauss ◽  
John R. Endres ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Toxicity Study ◽  
Developmental Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Sprague Dawley Rats ◽  
Chromosomal Aberration Test ◽  
Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

scholarly journals Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

2013 ◽  
Vol 82 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Organ Bath ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

Metabolism of triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways

1993 ◽  
Vol 41 (1) ◽  
pp. 141-147 ◽  
Author(s):  
Amy G. Hackett ◽  
John J. Kotyk ◽  
Hideji. Fujiwara ◽  
Eugene W. Logusch
Keyword(s):  
Metabolic Pathways ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals TRANSFERSOME GEL FORMULATION OF AN ETHANOL EXTRACT OF APPLES (MALUS DOMESTICA MILL) CONTAINING ANTIOXIDANTS AND IN VITRO PENETRATION TESTING USING FRANZ DIFFUSION CELLS

2017 ◽  
Vol 9 ◽  
pp. 32 ◽  
Author(s):  
Nurarita Fadila Zesiorani ◽  
Effionora Anwar
Keyword(s):  
Ethanol Extract ◽  
Sprague Dawley ◽  
Diffusion Cells ◽  
Sprague Dawley Rats ◽  
Apple Peel ◽  
Franz Diffusion Cells ◽  
Drug Efficiency ◽  
And Control ◽  
Peel Extract

Objective: This study aims to formulate and characterize a transfersome apple peel extract, formulate it into a gel, and compare it with a control gelmade without transfersome.Methods: Both gels were evaluated, stability tested, and penetration tested using Franz diffusion cells on the skin of female Sprague-Dawley rats. Thetransfersome preparations were formulated with different concentrations of the active substance, quercetin: 0.5% (F1); 0.7% (F2), and 1.0% (F3).Results: Based on the characterization results, F1 was selected as the optimum gel formulation because it had spherical morphology, a Dmean volume of106.44±2.70 nm, a polydispersity index of 0.078±0.01, a zeta potential of −49.96±2.05 mV, and a drug efficiency entrapment percentage of 78.78±0.46%.The cumulative amount of quercetin that was penetrated with the transfersome gel was 1514.41±26.31 μg/cm2, whereas the penetration with thecontrol gel extract was 1133.62±18.96 μg/cm2. The cumulative percentages of the penetrated gel transfersome and gel extract were 78.40±1.89%and 49.89±0.88%, respectively. The fluxes of transfersome gel and control gel extract were 52.33±0.11 μg/cm²/hrs and 40.89±0.68 μg/cm²/hrs,respectively.Conclusions: Based on these results, it can be concluded that the gel with transfersome exhibited better penetration than the gel extract alone.

Effects of androgens on bioactivity and immunoreactivity of pituitary FSH in GnRH antagonist-treated male rats

1990 ◽  
Vol 122 (2) ◽  
pp. 168-174 ◽  
Author(s):  
Om P. Sharma ◽  
Shafiq A. Khan ◽  
Gerhard F. Weinbauer ◽  
Mohammed Arslan ◽  
Eberhard Nieschlag
Keyword(s):  
Isoelectric Focusing ◽  
Gnrh Antagonist ◽  
Molecular Composition ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Combined Administration ◽  
Ph Range ◽  
Fsh Bioactivity

Abstract The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 μg/day by osmotic minipumps; sc), testosterone-filled Silastic implants (3×5 cm, sc), dihydrotestosterone-filled Silastic implants (3×5 cm, sc), E2 benzoate (15 μg/day, sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotesterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH. No significant differences were found in the isoelectric-focusing profiles or bioactivity to immunoreactivity ratios of pituitary FSH in animals treated with testosterone alone or in combination with antagonist. The results demonstrate that testosterone not only maintained the synthesis of both bioactive and immunoreactive FSH in male rats, but also influences the molecular composition of pituitary FSH. These effects of testosterone on pituitary FSH appear not to be mediated through hypothalamic GnRH.

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