The influence of doxazosin, an α1-adrenergic receptor antagonist on the urinary bladder contractility in pigs

2014 ◽  
Vol 17 (3) ◽  
pp. 527-529 ◽  
Author(s):  
W. Markiewicz ◽  
A. Jasiecka ◽  
D. Barski ◽  
J. Janiuk ◽  
A. Bossowska ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Adrenergic Receptor ◽  
Treated Group ◽  
Control Group ◽  
Detrusor Smooth Muscle ◽  
Before And After ◽  
Term Administration

Abstract In the present study influence of doxazosin on the porcine urinary bladder contractility has been examined. Immature pigs were treated for 30 days with: a) doxazosin (n = 5) per os at a dose of 0.1 mg/kg b.w. or b) placebo (n = 5; control group). Thereafter, animals were sacrificed and urinary bladder strips from the trigone were suspended in organ baths. The tension of the smooth musce was measured before and after exposition to acetylocholine (ACh; 10-5 - 10-3 M), norepinephrine (NE; 10-9 - 10-7 M) and 5-hydroxytryptamine (5-HT; 10-7 - 10-5 M). Both the ACh and 5-HT at the highest doses significantly increased the contractility in each group, but this response was weaker in doxazosin-treated animals. NE caused relaxation in both groups, but the effect was weaker in doxazosine-treated group. The results of our study have shown that long-term administration of doxazosin caused a desensitization of the detrusor smooth muscle for in vitro applied mediators of the autonomic nervous systems.

The RPMI-1640 vitamin mixture promotes bovine blastocyst development in vitro and downregulates gene expression of TXNIP with epigenetic modification of associated histones

2017 ◽  
Vol 9 (1) ◽  
pp. 87-94 ◽  
Author(s):  
S. Ikeda ◽  
M. Sugimoto ◽  
S. Kume
Keyword(s):  
Polymerase Chain Reaction ◽  
Treated Group ◽  
Preimplantation Embryos ◽  
Control Group ◽  
Chain Reaction ◽  
Blastocyst Development ◽  
Polymerase Chain ◽  
Vitamin Mixture

Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short- and long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker for preimplantation stress that is implicated in in vitro fertilization- (IVF) induced long-term DOHaD effects. B vitamins, as participants in one-carbon metabolism, may affect preimplantation embryos by epigenetic alterations of metabolically and developmentally important genes. In vitro-produced bovine embryos were cultured with or without Roswell Park Memorial Institute 1640 vitamin mixture, containing B vitamins and B vitamin-like substances, from day 3 after IVF and we evaluated blastocyst development and TXNIP messenger RNA (mRNA) expression in the blastocysts by reverse transcription-quantitative polymerase chain reaction. The degree of trimethylation of histone H3 lysine 27 (H3K27me3) at TXNIP promoter was examined semi-quantitatively by chromatin immunoprecipitation polymerase chain reaction. Total H3K27me3 were also compared between the groups by Western blot analysis. The vitamin treatment significantly increased the rates of blastocyst development (P<0.05) and their hatching (P<0.001) from the zona pellucida by day 8. The mRNA expression of TXNIP was lower (P<0.01) in blastocysts in the vitamin-mixture-treated group concomitant with higher (P<0.05) level of H3K27me3 of its promoter compared with the control group. The total H3K27me3 in the vitamin-mixture-treated group was also higher (P<0.01) than that in the control group. The epigenetic control of genes related to important metabolic processes during the periconceptional period by nutritional conditions in utero and/or in vitro may have possible implication for the developmental programming during this period that may impact the welfare and production traits of farm animals.

Apelin-13 deteriorates hypertension in rats after damage of the vascular endothelium by ADMA

2013 ◽  
Vol 91 (9) ◽  
pp. 708-714 ◽  
Author(s):  
Xue Han ◽  
Dong-Liang Zhang ◽  
Dao-Xin Yin ◽  
Qi-Dong Zhang ◽  
Wen-Hu Liu
Keyword(s):  
Endothelial Dysfunction ◽  
Treated Group ◽  
Control Group ◽  
Transmission Electron ◽  
Before And After ◽  
Pass Through ◽  
Mlc Phosphorylation ◽  
And Control

Asymmetric dimethylarginine (ADMA) is a risk factor for endothelial dysfunction. The polypeptide apelin has biphasic effects on blood vessels in vivo and in vitro. We investigated the effect of apelin-13 on ADMA-damaged vessels. Rats were divided among ADMA-treated and control groups, which were treated with ADMA (10 mg·(kg body mass)−1·day−1) or saline, respectively, for 4 weeks. Systolic blood pressure (SBP) was measured before and after the injection of apelin-13. The ultrastructure of endothelial cells in caudal arteries was examined using transmission electron microscopy. The reactivities of isolated caudal artery rings were observed after exposure to apelin-13, and myosin light chain (MLC) phosphorylation was assessed by immunohistochemistry in rings treated with or without apelin-13. ADMA induced hypertension and endothelial dysfunction. After injection of apelin-13, SBP declined in the control group but was elevated in the ADMA-treated group. In vitro, apelin-13 caused relaxation in rings in the control group, but it contracted rings in the ADMA-treated group. Apelin-13 promoted MLC phosphorylation in vascular smooth muscle cells (VSMCs) in the ADMA group. These results indicate that apelin-13 might pass through ADMA-damaged endothelium and act on VSMCs to increase MLC phosphorylation, thus contributing to vasoconstriction and exacerbating hypertension.

The influence of doxazosin on the contractility of the urinary bladder in female pigs with experimentally induced cystitis

2017 ◽  
Vol 20 (3) ◽  
pp. 485-490
Author(s):  
W. Markiewicz ◽  
A. Bossowska ◽  
E. Lepiarczyk ◽  
M. Majewski ◽  
P. Radziszewski ◽  
...  
Keyword(s):  
Body Weight ◽  
Urinary Bladder ◽  
Smooth Muscles ◽  
Treated Group ◽  
Control Group ◽  
Group I ◽  
Group Ii ◽  
Experimental Group ◽  
Experimentally Induced

Abstract The present in vitro study investigated the influence of doxazosin on the contractility of the urinary bladder in female pigs with experimentally induced cystitis. Fifteen juvenile female piglets (18-20 kg body weight) were randomly assigned into three groups (n=5 animals each): i) control (clinically healthy animals, without doxazosin treatment), ii) animals with induced inflammation of the urinary bladder, but without doxazosin treatment (experimental group I) and iii) animals with inflamed bladder, treated orally with doxazosin (0.1 mg/kg body weight for 30 days; experimental group II). Thereafter, the pigs were sacrificed and strips of the bladder trigone were suspended in organ baths. The tension and amplitude of the smooth muscles was measured before and after exposition to 5-hydroxytryptamine (5-HT; 10-6-10-4 M), acetylocholine (ACh; 10-5-10-3 M) and norepinephrine (NE; 10-9-10-7 M). 5-HT caused an increase in the tension of contractions in all the groups and the amplitude in the experimental groups, however, the effect was higher in the experimental group I than in group II as compared to that found in the pre-treatment period. ACh caused an increase in the tension in the control group and a decrease in the amplitude in both experimental groups; these changes significantly differed between the control and doxazosin-treated group. NE caused a decrease in the tension in both experimental groups and amplitude in all the groups, however, the effect was most strongly expressed in doxazosine-treated group. The present study has revealed that long-term administration of doxazosin causes a desensitization of the detrusor smooth muscle to in vitro applied mediators in the autonomic nervous system.

Regulation of renin release and renal hemodynamics during acute and chronic verapamil administration

1990 ◽  
Vol 258 (4) ◽  
pp. F1105-F1109
Author(s):  
D. B. Young ◽  
H. B. Lin ◽  
J. K. LeDuff
Keyword(s):  
Perfusion Pressure ◽  
Treated Group ◽  
Renal Hemodynamics ◽  
Renin Release ◽  
Control Group ◽  
Calcium Entry Blocker ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term

The effects of short- and long-term administration of the calcium-entry blocker verapamil on regulation of renal hemodynamics and renin release were analyzed in anesthetized dogs at controlled levels of renal perfusion pressure between 110 and 60 mmHg. The following three groups of dogs were studied: a control group, an acutely treated verapamil group (initial dose of 150 micrograms/kg followed by 4 micrograms.kg-1.min-1), and a chronically treated verapamil group (240 mg per os twice each day). At 110 mmHg the renal blood flow (RBF) in the acutely and chronically treated groups was 53% greater than (P less than 0.03) and 79% greater than (P less than 0.01) that of the control group. Glomerular filtration rate (GFR) in the acutely and chronically treated groups was 64 and 92%, respectively, greater than (P less than 0.01 for both) that of the control group. Autoregulation of RBF and GFR was extremely effective in the control group, whereas it was severely impaired by acute and long-term treatment with verapamil. Renin release at 110 mmHg in the control and the acutely treated groups were similar, 3.36 +/- 0.96 and 4.46 +/- 0.64 U.min-1.g-1, respectively, although in the chronically treated group the rate of release was 8.89 +/- 2.60 U.min-1.g-1 (P less than 0.03). As perfusion pressure was reduced, the rate of release from the acutely treated group rose to higher levels than that of the control group; at 70 mmHg release from the acutely treated group was 88% greater than that of the control group (P less than 0.01). Verapamil profoundly alters regulation of renal hemodynamics and renin release and the effect is prominent during both short- and long-term administration.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

scholarly journals Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Malinee Thanee ◽  
Sureerat Padthaisong ◽  
Manida Suksawat ◽  
Hasaya Dokduang ◽  
Jutarop Phetcharaburanin ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Treated Group ◽  
Control Group ◽  
High Recurrence Rate ◽  
Nucleic Acid Metabolism ◽  
In Vivo Models ◽  
Tryptophan Degradation ◽  
Xenograft Mice

Abstract Background Sulfasalazine (SSZ) is widely known as an xCT inhibitor suppressing CD44v9-expressed cancer stem-like cells (CSCs) being related to redox regulation. Cholangiocarcinoma (CCA) has a high recurrence rate and no effective chemotherapy. A recent report revealed high levels of CD44v9-positive cells in CCA patients. Therefore, a combination of drugs could prove a suitable strategy for CCA treatment via individual metabolic profiling. Methods We examined the effect of xCT-targeted CD44v9-CSCs using sulfasalazine combined with cisplatin (CIS) or gemcitabine in CCA in vitro and in vivo models and did NMR-based metabolomics analysis of xenograft mice tumor tissues. Results Our findings suggest that combined SSZ and CIS leads to a higher inhibition of cell proliferation and induction of cell death than CIS alone in both in vitro and in vivo models. Xenograft mice showed that the CD44v9-CSC marker and CK-19-CCA proliferative marker were reduced in the combination treatment. Interestingly, different metabolic signatures and significant metabolites were observed in the drug-treated group compared with the control group that revealed the cancer suppression mechanisms. Conclusions SSZ could improve CCA therapy by sensitization to CIS through killing CD44v9-positive cells and modifying the metabolic pathways, in particular tryptophan degradation (i.e., kynurenine pathway, serotonin pathway) and nucleic acid metabolism.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Decreased neuronal inhibition in vitro after long-term administration of ethanol

Science ◽  
1984 ◽  
Vol 224 (4655) ◽  
pp. 1359-1361 ◽  
Author(s):  
D Durand ◽  
P. Carlen
Keyword(s):  
Neuronal Inhibition ◽  
Term Administration

scholarly journals Cystitis increases colorectal afferent sensitivity in the mouse

2009 ◽  
Vol 297 (6) ◽  
pp. G1250-G1258 ◽  
Author(s):  
Pablo Rodolfo Brumovsky ◽  
Bin Feng ◽  
Linjing Xu ◽  
Carly Jane McCarthy ◽  
G. F. Gebhart
Keyword(s):  
Urinary Bladder ◽  
Treated Group ◽  
Mechanical Sensitivity ◽  
Pelvic Nerve ◽  
Treatment Groups ◽  
Colon Inflammation ◽  
Afferent Fibers ◽  
Peripheral Mechanism ◽  
Inflammatory Soup

Studies in humans and rodents suggest that colon inflammation promotes urinary bladder hypersensitivity and, conversely, that cystitis contributes to colon hypersensitivity, events referred to as cross-organ sensitization. To investigate a potential peripheral mechanism, we examined whether cystitis alters the sensitivity of pelvic nerve colorectal afferents. Male C57BL/6 mice were treated with cyclophosphamide (CYP) or saline, and the mechanosensitive properties of single afferent fibers innervating the colorectum were studied with an in vitro preparation. In addition, mechanosensitive receptive endings were exposed to an inflammatory soup (IS) to study sensitization. Urinary bladder mechanosensitive afferents were also tested. We found that baseline responses of stretch-sensitive colorectal afferents did not differ between treatment groups. Whereas IS excited a proportion of colorectal afferents CYP treatment did not alter the magnitude of this response. However, the number of stretch-sensitive fibers excited by IS was increased relative to saline-treated mice. Responses to IS were not altered by CYP treatment, but the proportion of IS-responsive fibers was increased relative to saline-treated mice. In bladder, IS application increased responses of muscular afferents to stretch, although no differences were detected between saline- and CYP-treated mice. In contrast, their chemosensitivity to IS was decreased in the CYP-treated group. Histological examination revealed no changes in colorectum and modest edema and infiltration in the urinary bladder of CYP-treated mice. In conclusion, CYP treatment increased mechanical sensitivity of colorectal muscular afferents and increased the proportion of chemosensitive colorectal afferents. These data support a peripheral contribution to cross-organ sensitization of pelvic organs.

Sign in / Sign up

Export Citation Format

Share Document