Portal hypertension increases vasoconstrictor responsiveness of rat aorta

1999 ◽  
Vol 96 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Claire CONNOLLY ◽  
Teresa CAWLEY ◽  
P. Aiden MCCORMICK ◽  
James R. DOCHERTY

We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague–Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71±0.12 ;g) and noradrenaline (1.00±0.17 ;g) but not phenylephrine (0.86±0.10 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45±0.04 ;g, 0.57±0.07 ;g, 0.71±0.05 ;g respectively). In aortas from Sprague–Dawley rats, the maximum response to KCl (1.21±0.21 ;g) and phenylephrine (1.54±0.30 ;g) but not noradrenaline (0.93±0.09 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59±0.09 ;g, 0.76±0.11 ;g, 1.04±0.10 ;g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [3H]prazosin to α1-adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague–Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.


2009 ◽  
Vol 87 (8) ◽  
pp. 602-609 ◽  
Author(s):  
Laura L. Atkinson ◽  
Brian G. Topp ◽  
Jenny Au ◽  
Horatiu V. Vinerian ◽  
Narinder Dhatt ◽  
...  

β-cell mass dynamics play an important role in the adaptation to obesity, as well as in the pathogenesis of type 2 diabetes. Here we used a 24-hour modified hyperglycemic clamp protocol to investigate the effect of increasing glucose concentrations (15, 20, 25, or 35 mmol/L) on β-cell mass and rates of β-cell replication, death, and neogenesis in 6-week-old Sprague Dawley rats (n = 40). During the first 4 h of glucose infusion, plasma insulin levels rose to an approximate steady state in each group, but by the end of 24 h, there was no difference in insulin levels between any of the groups. There was also no difference in β-cell mass between groups. Mean β-cell replication rates displayed a linear relationship to mean plasma glucose levels in all hyperglycemic animals (r2 = 0.98, p < 0.05). Relative to the uninfused basal control animals, replication rates were significantly reduced in the 15 mmol/L glucose group. The percentage of TUNEL-positive β-cells was not different between groups. There was also no significant difference in markers of neogenesis. Thus, these data demonstrate that hyperglycemia for 24 h had no effect on β-cell mass, death, or neogenesis in 6-week-old Sprague Dawley rats. We demonstrate a linear relationship, however, between hyperglycemia and β-cell replication rates in vivo.


1960 ◽  
Vol 38 (3) ◽  
pp. 187-192 ◽  
Author(s):  
Joyce L. Beare ◽  
T. K. Murray ◽  
J. A. Campbell

Wistar and Sprague–Dawley rats were compared in their response to 20% rapeseed oil or corn oil in a basal diet of ground fox cubes. Apparent coefficients of digestibility were significantly lower for rapeseed oil than for corn oil in the Sprague–Dawley, but not in the Wistar rats. After 6 weeks the adrenals of Sprague–Dawley rats were larger in the animals fed rapeseed oil than in those fed corn oil, while the adrenals of Wistar rats were not influenced by the dietary oil. These strain differences explain some discrepancies appearing in the literature concerning the effects of rapeseed oil in the rat.In another experiment, Wistar and Sprague–Dawley rats deprived of vitamin A for 18 days were fed a purified basal diet with 20% rapeseed oil or corn oil and dosed with 75 or 150 I.U. of vitamin A per day. After 14 days there was no significant effect of the strain of rat or the type of dietary oil on the liver storage of vitamin A. The rate of depletion of vitamin A from the liver following a single dose of 1200 I.U. of vitamin A was also studied and indicated no significant difference attributable to the dietary oils.


1960 ◽  
Vol 38 (1) ◽  
pp. 187-192 ◽  
Author(s):  
Joyce L. Beare ◽  
T. K. Murray ◽  
J. A. Campbell

Wistar and Sprague–Dawley rats were compared in their response to 20% rapeseed oil or corn oil in a basal diet of ground fox cubes. Apparent coefficients of digestibility were significantly lower for rapeseed oil than for corn oil in the Sprague–Dawley, but not in the Wistar rats. After 6 weeks the adrenals of Sprague–Dawley rats were larger in the animals fed rapeseed oil than in those fed corn oil, while the adrenals of Wistar rats were not influenced by the dietary oil. These strain differences explain some discrepancies appearing in the literature concerning the effects of rapeseed oil in the rat.In another experiment, Wistar and Sprague–Dawley rats deprived of vitamin A for 18 days were fed a purified basal diet with 20% rapeseed oil or corn oil and dosed with 75 or 150 I.U. of vitamin A per day. After 14 days there was no significant effect of the strain of rat or the type of dietary oil on the liver storage of vitamin A. The rate of depletion of vitamin A from the liver following a single dose of 1200 I.U. of vitamin A was also studied and indicated no significant difference attributable to the dietary oils.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.


Author(s):  
G. Ilse ◽  
K. Kovacs ◽  
N. Ryan ◽  
T. Sano ◽  
L. Stefaneanu ◽  
...  

Germfree state and food restriction have been shown to increase life span and delay tumor occurrence in rats. We report here the histologic, immunocytochemical and electron microscopic findings of adenohypophyses of aging, male Lobund-Wistar rats raised at Lobund Laboratories. In our previous study, the morphologic changes in the adenohypophyses of old rats have been extensively investigated by histology, immunocytochemistry and electron microscopy. Lactotroph adenomas were frequent in Long-Evans and Sprague-Dawley rats, whereas gonadotroph adenomas were frequent in Sprague-Dawley and Wistar rats.Male Lobund-Wistar rats were divided into four groups: 1) conventional, which were raised under normal non-germfree environment and received food ad libitum; 2) germfree-food ad libitum; 3) conventional environment-food restricted and 4) germfree-food restricted. The adenohypophyses were removed from 6-month-, 18-month- and 30-month-old rats. For light microscopy, adenohypophyses were fixed in formalin and embedded in paraffin.


Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal

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.


1978 ◽  
Vol 58 (4) ◽  
pp. 743-752 ◽  
Author(s):  
J. J. KENNELLY ◽  
F. X. AHERNE ◽  
A. J. LEWIS

Forty-eight crossbred pigs of average initial weight 21 kg were fed 10% Tower rapeseed meal (RSM) and 10% Candle RSM as partial replacements for soybean meal (SBM). Diets were formulated to be isocaloric. Pigs fed the SBM diet consumed less feed, gained significantly (P < 0.01) faster and were more efficient at converting feed to gain than those fed the RSM diets. Performance of pigs fed Candle RSM was not significantly different to that obtained with Tower RSM. In a second experiment, dehulled Tower RSM and Tower RSM hulls were mixed in amounts to produce RSM with crude fibre levels of 6.8, 10.8, 13.5 and 15.8%. The simulated RSM and Tower and Candle RSM were used to completely replace SBM in the diets of weanling (75 g) Sprague-Dawley rats. Rats fed SBM had significantly (P < 0.05) higher average daily gain (ADG) than those fed Tower or Candle RSM, or diets containing the rapeseed meats. There was no significant (P < 0.05) difference in ADG, feed intake or feed to gain ratio of rats fed either Tower or Candle RSM. Feed intake, feed to gain ratio and fecal volatile fatty acid concentrations increased while average daily gain decreased with increasing level of hulls in simulated RSM diets. There was no significant difference (P < 0.05) in thyroid weight between rats fed SBM, Tower RSM or Candle RSM.


1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio

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.


Sign in / Sign up

Export Citation Format

Share Document