Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RATS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1994

Hypertension in the transgenic rat TGR(mRen-2)27 may be due to enhanced kinetics of the reaction between mouse renin and rat angiotensinogen.

The transgenic rat TGR(mRen-2)27, in which the Ren-2 mouse renin gene is transfected into the genome of the rat, develops severe hypertension with high adrenal renin and low kidney renin. These animals express both mouse and rat renin. To investigate the cause of hypertension in the TGR rat, we compared the kinetics of mouse renin acting on mouse and rat angiotensinogens. The optimum pH of the renin reaction in the Sprague-Dawley rat was 6.5, whereas the optimum pH of the reaction in the TGR rat was approximately 8.5. The optimum pH of the renin reaction in the DBA mouse was 6.0. Purified mouse Ren-2 renin acting on rat angiotensinogen showed a pH profile similar to that for the renin reaction in the TGR rat. The angiotensinogen concentration in pooled plasma from eight DBA mice was 104.5 ng angiotensin I/mL and was clearly lower than that in Sprague-Dawley rats (772.4 +/- 37.3 ng angiotensin I/mL, n = 4). The reaction of purified mouse Ren-2 renin with rat angiotensinogen was 10 times faster than with mouse angiotensinogen. Plasma renin activity in DBA mice increased dramatically on addition of rat angiotensinogen (from 253.4 +/- 66.7 to 225,000 +/- 48,000 ng angiotensin I/mL per hour). Intravenous injection of 2 or 10 microL of DBA mouse plasma into the nephrectomized Sprague-Dawley rat increased the mean arterial pressure of the rat by 27.7 +/- 4.7 and 61.8 +/- 2.7 mmHg, respectively, whereas injection of 200 microL of Sprague-Dawley rat plasma did not change the mean arterial pressure of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗
PubMed1991

Adenocarcinoma in the ascending colon of ACI strain rat foster bred by WF-Osaka female rat.

We now keep HFRSV free WF-Osaka rats and ACI rats together in the separate three animal rooms (animal room 1, 2 and 3) and the incidence of colon carcinoma is still high on the WF-Osaka rats in animal room 1 with the high humidity. Two female ACI rats developed colon carcinomas in the ascending colon. The gross and the histological appearance of the colon carcinoma were completely the same as those of WF-Osaka rats. ACI and WF-Osaka rat strain together have been kept bred in neighborhood of each other in different racks in the identical animal room 1. To obtain HFRSV free ACI rat strain, Antecedents born by cesarean section of ACI female pregnant rat were foster-bred by WF-Osaka female nursing rat incidentally, and at the fourth mating generation after the start of foster-breeding, they developed colon carcinomas at the age of four months. Before five out of eight F1 hybrids by WF-Osaka cancer carrying female rat x male ACI rat had developed the same colon carcinoma, but none of F1 hybrids by the contrary mating had developed colon carcinomas in this same animal room 1. Animal room 1 and 2 where there was a high incidence of colon carcinomas, had happened to be kept moistened. However, after disinfection of these animal rooms, the animal room 2 and 3 occurred to be kept dried, and rats of WF-Osaka strain ceased to develop colon carcinomas in the animal room 2. Thereafter, animal room 2 and 3 were adjusted to be kept moistened again. Subsequently WF-Osaka rats in the animal room 2 began to have colon carcinomas in the ascending colon as before, but none of rats developed colon carcinomas in the animal room 3. Based on these findings, we consider that milk factor at the time of foster-breeding played an important role first and high moistened condition of the animal room resulted in promoting effect on colon carcinogenesis on ACI rats and WF-Osaka rats as well.

Adenocarcinoma↗
PubMed1979

Further characterization of growth hormone-dependent somatomedin-binding proteins in rat serum and demonstration of somatomedin-binding proteins produced by rat liver cells in culture.

The somatomedin-like peptide multiplication-stimulating activity (MSA) binds specifically to rat serum. The pattern of MSA binding is GH dependent. Specific binding of [125I]iodo-MSA in normal rat serum is primarily in the gamma-globulin region (peak II) on Sephadex G-200, while MSA binding in hypophysectomized (hypox) rat serum is near the albumin region (peak III). This study further characterizes the peak II and peak III somatomedin-binding proteins produced by rat liver cells in culture. [125I]Iodo-MSA binding to normal rat serum is abolished by trypsin pretreatment of rat serum, suggesting that MSA binds to protein components of serum. The only detectable somatomedin activity (measured by [3H]thymidine incorporation into chick embryo fibroblast DNA) in fractions of normal rat serum chromatographed on Sephadex G-200 coincides with peak II binding of [125I]iodo-MSA. In hypox rat serum, the majority of detectable somatomedin activity is in the peak III region. There is complete displacement of the human somatomedins [125I]iodoinsulin-like growth factor I and II and [125I]iodosomatomedin A from the rat serum-binding sites by unlabeled MSA, suggesting that the human somatomedins bind to the same sites as MSA. Treatment of normal rat serum with 1 M acetic acid dissociates somatomedin activity from its binding proteins and converts somatomedin-binding proteins from peak II to peak III. Scatchard analysis of competitive binding data using [125I]iodo-MSA yields a binding affinity that is not appreciably different for either normal or hypox rat sera. The binding capacity of normal or acid-treated normal rat serum for MSA is significantly greater than that for comparably treated hypox rat sera. Although the site of synthesis of somatomedin-binding proteins in vivo is unknown, specific somatomedin-binding proteins are synthesized by two rat liver cell lines in culture. These rat liver cell somatomedin-binding proteins have the same molecular size and the same binding affinity for MSA as the peak III somatomedin-binding protein(s) in rat serum.

Animals↗
PubMed1988

Monoclonal antibodies specific for rat relaxin. I. Production and characterization of monoclonal antibodies that neutralize rat relaxin's bioactivity in vivo.

The physiological role of relaxin during pregnancy and at parturition in the rat is not absolutely established. There are limitations to the experimental approach used in the few studies that examined the influence of relaxin in the pregnant rat. These studies were unphysiological, since they involved administration of porcine relaxin as well as progesterone and estrogen to ovariectomized pregnant rats. A more physiological approach is to use antibodies to neutralize the biological actions of endogenous relaxin in the intact pregnant rat. The purpose of the present study was to produce and characterize monoclonal antibodies suitable for this approach. Six stable and rapidly growing hybridoma clones which produced monoclonal antibodies specific for rat relaxin (MCA-rR) were obtained after the fusion of NSO mouse myeloma cells with lymphocytes from the spleen of a BALB/c mouse immunized with rat relaxin. Five MCA-rR (MCA1-5; all immunoglobulin G1 kappa) inhibited the ability of exogenously administered rat relaxin to increase the interpubic ligament length in estrogen-primed mice. Of the five MCA-rR that neutralized rat relaxin's bioactivity in vivo, MCA1 exhibited the highest relative affinity for rat relaxin. MCA1 was also highly specific for rat relaxin. MCA1 demonstrated no cross-reactivity with rat insulin, rat insulin-like growth factor I and II, or porcine relaxin-proteins that are structurally related to rat relaxin. In view of its high affinity and high specificity for rat relaxin as well as its ability to neutralize rat relaxin's bioactivity in vivo, MCA1 was selected for use in subsequent studies aimed at the neutralization of endogenous relaxin in intact pregnant rats.

Animals↗
PubMed1993

Pharmacokinetics and pharmacodynamics of bumetanide after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt induced hypertensive rats.

The pharmacokinetics and pharmacodynamics of bumetanide were investigated after intravenous (i.v.) administration, 10 mg kg-1, and oral administration, 20 mg kg-1, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt induced hypertensive rats (DOCA-salt rats). After i.v. administration, the pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between SHRs and the control Wistar rats. Similar results were also shown between DOCA-salt rats and the control Sprague-Dawley (SD) rats. After oral administration, the AUC0-12 h decreased significantly (186 versus 335 micrograms min ml-1) in SHRs and this resulted in decreased F(15.4 versus 23.6 and 2.78 versus 5.76% using two equations) in SHRs when compared with the control Wistar rats, although none of the other pharmacokinetic parameters varied significantly between SHRs and Wistar rats. This effect seemed to be due to the decreased enterohepatic recirculation of bumetanide in SHRs: the amounts of both bumetanide and its glucuronide product, which are capable of enterohepatic recirculation, excreted in 8 h bile juice decreased significantly in SHRs (11.3 versus 37.4 micrograms as expressed in terms of bumetanide) when compared with Wistar rats. The pharmacodynamic parameters did not vary significantly between SHRs and Wistar rats after oral administration of bumetanide. The pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between DOCA-salt rats and SD rats after oral administration of the drug. The liver weights compared to body weight increased significantly in SHRs when compared with Wistar rats and the corresponding values for the kidney increased significantly in DOCA-salt rats when compared with SD rats.

Administration, Oral↗
PubMed2006

Lewis rats are more sensitive than Fischer rats to successive negative contrast, but less sensitive to the anxiolytic and appetite-stimulating effects of chlordiazepoxide.

Lewis rats show greater anticipatory contrast effects than Fischer 344 rats. Specifically, relative to Fischer rats, Lewis rats exhibit greater avoidance of a saccharin cue when it predicts the future availability of a preferred sucrose reward [Grigson, P.S., Freet, C.S. The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: evidence for the reward comparison hypothesis. Behav Neurosci 2000;114:353-363.]. Experiment 1 was designed to determine whether Lewis rats also would demonstrate greater contrast in another paradigm, successive negative contrast (SNC). The results demonstrated a tendency for greater SNC in Lewis rats and then slower recovery from the unexpected loss of reward relative to the Fischer rats. Pretreatment with the anxiolytic agent, chlordiazepoxide (CDP), effectively eliminated contrast in the Fischer rats, but served to prolong recovery from contrast in the Lewis rats. Finally, the results of Experiment 2 demonstrated that Fischer rats, but not Lewis rats, increase consumption of a 0.1 M sucrose solution following pretreatment with CDP. Together, the results show that, while both Lewis and Fischer rats demonstrate SNC, the effect is more sustained in the Lewis rats and these rats are insensitive to both the anxiolytic and the appetite-stimulating effects of CDP.

Animals↗
PubMed1994

Abnormal accumulation of copper-metallothionein in the liver and kidney of Long-Evans rats with a cinnamon-like coat color (LEC rats).

We determined the copper (Cu) and metallothionein (MT) concentrations in the liver and kidney supernatants of Long-Evans rats with a cinnamon-like coat color (LEC rats), and also measured the Cu and MT levels in the serum of these rats. Seven-week-old rats had abnormally high levels of both substances in the liver. The levels in the liver supernatant were over 80- and 16-fold higher, respectively, in LEC rats than in normal 7-week-old Wistar rats. LEC rats suffering from acute hepatitis or hepatoma had a much higher level of hepatic MT, but the Cu level was higher only in the liver of those with hepatoma. The serum levels of Cu and MT in LEC rats with acute hepatitis were more than 10-fold higher than those in normal LEC rats. These levels were decreased in the rats with chronic hepatitis or hepatoma. In the liver of LEC rats with hepatoma, the area of hepatocellular carcinoma and of noncancerous liver showed over twice higher Cu and MT levels than the area of cholangiofibrosis. The Sephadex G-75 elution profile from the liver supernatant of a normal LEC rat showed that the peak of Cu closely corresponded to that of MT recognized with anti-MT antiserum. The levels of Cu and MT in the kidney supernatant of LEC rats with acute hepatitis were more than 25-fold higher than in that of normal LEC rats. However, there were no marked increases in the levels in the kidney supernatant of LEC rats with chronic hepatitis or hepatoma.

Animals↗
PubMedDate not supplied

Intraperitoneal administration of ascorbic acid delays the turnover of 3H-labelled cortisol in the plasma of an ODS rat, but not in the Wistar rat. Evidence in support of the cardinal role of vitamin C in the progression of glucocorticoid synthesis.

The purpose of this investigation was to reproduce in rats the enhancing effect of vitamin C on adrenal glucocorticoid production, a phenomenon that has been repeatedly observed in our human experiments. Here, we tried to assess the impact of vitamin C pretreatment on the turnover of exogenous 3H-labelled cortisol tracer in rats. 500 mg ascobic acid in 15 ml isotonic liquid per rat was administered intraperitoneally into rats of the experimental group, and 15 ml physiological saline per rat was similarly introduced into rats of the control group. At various times after the loading of either vitamin C or saline, 3H-labelled cortisol, 20 muc/0.5 ml saline/rat, was injected subcutaneously into rats of both the experimental and control groups. Thirty minutes later, all rats were sacrificed by exsanguination, and the radioactivity content was measured in the lipophilic fractions as well as in the purified corticosteroid compounds of blood, adrenal, testis and liver samples. To test the specificity of vitamin C action, experimental results from scurvy-prone ODS rats were compared with those of scurvy-resistant Wistar rats. Results obtained are as follows: a) the practice of vitamin C loading markedly delayed the turnover of 3H-cortisol in both the plasma lipophilic fraction and the plasma cortisol fraction, a finding which indicates that the above vitamin C pretreatment enhanced the release of endogenous glucocorticoid in such as to delay the turnover of the tracer cortisol in plasma. b) The above "dilution" effect of endogenous glucocorticoid surge was very distinct in both the lipophilic fraction and the cortisol fraction of ODS rats, and was less distinct (lipophilic fraction) or insignificant (cortisol fraction) in Wistar rats, a finding to indicate that the observed effect of vitamin C was of physiological significance. c) The responses of the adrenal glands, testes and liver to vitamin C pretreatment were generally more distinct in ODS rats than in Wistar rats, but varied from one organ to another. The significance of the functional linkage between vitamin C and adrenal glucocorticoid, which has been confirmed both in both the humans and rats in our laboratory, was discussed in the light of the historical development of vitamino-endocrinology.

Adrenal Glands↗
PubMed1994

The receptor with high affinity for IgE on rat mast cells is a functional receptor for rat IgG2a.

Rat mast cells express high-affinity receptors for IgE (Fc epsilon RI) and low-affinity receptors for IgG (Fc gamma R). In this study, the capacity of IgG to activate the rat basophilic leukemia (RBL-2H3) and rat peritoneal mast cells was investigated. Immune complexes formed with purified rat IgG and antigen as well as chemically cross-linked rat IgG induced histamine release from RBL-2H3 cells. This stimulation was inhibited by pre-incubation of the cells with saturating concentrations of monomeric IgE. With chemically cross-linked rat IgG of each subclass, only IgG2a stimulated histamine release from RBL-2H3 cells and this release was also inhibited by prior saturation of the Fc epsilon RI with monomeric IgE. Identical results were obtained with rat peritoneal mast cells. In binding experiments, IgE and cross-linked rat IgG2a bound to rat Fc epsilon RI transfected into CHO cells. Monomeric rat IgG2a, cross-linked rat IgG1, IgG2b, IgG2c and rabbit IgG did not bind to Fc epsilon RI. Stimulation of RBL-2H3 cells with aggregated IgG2a induced phosphorylation of tyrosines in the beta and gamma subunits of the Fc epsilon RI. Thus, although RBL-2H3 and rat peritoneal mast cells have Fc gamma R, the IgG-mediated stimulation of these cells for histamine release was by the Fc epsilon RI. Altogether, these data demonstrate that the rat Fc epsilon RI is a functional receptor with low affinity for rat IgG2a.

Animals↗
PubMed1996

NTP Toxicity Studies of 60-Hz Magnetic Fields Administered by Whole Body Exposure to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice.

Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz) and generally of low intensity. The prevailing view among physicists is that exposure to these low-frequency, low-intensity fields does not pose a health hazard. However, this view has been challenged by reports linking magnetic field exposure to the development of leukemia and other cancers. Because multiple epidemiologic studies suggested a potential for increased cancer rates with increasing exposure, and because of public concern, the effects of 60-Hz magnetic field exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body-exposure studies. Animals were evaluated for hematology and clinical chemistry (rats only) parameters, pineal gland hormone concentrations, and histopathology. Additional studies were performed in Sprague-Dawley rats to examine teratologic and reproductive effects of magnetic field exposure. In the 8-week toxicity studies, groups of male and female F344/N rats and B6C3F1 mice were exposed for 18.5 hours per day to 60-Hz magnetic fields at intensities of 0 (control), 0.02, 2, and 10 gauss (G). Additional groups of rats and mice were exposed to intermittent 10 G fields (1 hour on/1 hour off) for 18.5 hours per day. No evidence of toxicity associated with exposure to magnetic fields was observed in rats or mice. Clinical observations provided no evidence of adverse effects associated with magnetic field exposure. Compared to control rats and mice, there were no biologically significant differences in hematology or clinical chemistry parameters of rats exposed to magnetic fields. No gross lesions or histopathologic findings in rats or mice were attributed to exposure to 60-Hz magnetic fields. In addition, magnetic field exposure was not associated with a significant reduction in serum melatonin or pineal gland melatonin concentration, or pineal gland activity of N-acetyltransferase in either species. One female rat in the 2 G exposure group died during the 8-week toxicity study from causes unrelated to magnetic field exposure; all other male and female rats and mice in the study survived until the end of the study. Final mean body weights and mean organ weights of a few groups of exposed animals differed from those of the control groups; however, no clear pattern of magnetic field effects was observed, and these differences are not considered to be biologically significant. For the teratology study, groups of 55 pregnant female Sprague-Dawley rats were exposed to the same magnetic fields as in the toxicity study on gestation days 6 through 19. Fifteen pregnant females exposed to 85 mg ethylenethiourea/kg body weight served as positive controls. Except for the positive controls, there were no changes in maternal or fetal weights, nor were fetal abnormalities found. The number of pregnant females was significantly lower in groups exposed to magnetic fields than in the control group; however, all breeding in the teratology study was completed prior to the first day of magnetic field or sham exposure. On this basis, this finding is unrelated to magnetic field exposure. In addition, there were no differences between control and exposed groups in the number of pregnant females in the continuous breeding study, in which breeding took place within the magnetic fields. Groups of 40 breeding pairs of Sprague-Dawley rats were exposed to the same magnetic fields as in the toxicity study during the breeding and lactation of five litters in a continuous breeding study. The fifth litter was exposed during gestation and lactation; one male and one female from each litter were raised to sexual maturity receiving the same exposures as the parents; rats were mated to nonsibling rats and allowed to deliver the third-generation offspring. The results of the continuous breeding study demonstrated no effects of magnetic field exposure on reproductive performance in either male or female rats.

Journal Article↗
PubMed1994

Preservation of GLUT 2 expression in islet beta cells of Kilham rat virus (KRV)-infected diabetes-resistant BB/Wor rats.

Loss of GLUT 2, the glucose transporter isoform of pancreatic beta cells, has been reported to accompany the onset and perhaps contribute to the pathogenesis, of insulin-dependent and non-insulin-dependent diabetes mellitus in BB/Wor and Zucker fatty rats. In this study we investigated the effect of Kilham Rat Virus infection on GLUT2 expression in diabetes-resistant BB/Wor rats. Viral antibody-free diabetes-resistant rats do not develop spontaneous diabetes, but inoculation with Kilham Rat Virus induces autoimmune beta-cell destruction and hyperglycaemia. Pancreas sections from normoglycaemic diabetes-resistant BB/Wor rats were obtained 5, 7 and 25 days after inoculation with Kilham Rat Virus and stained for GLUT2 using a rabbit polyclonal antibody. At all time points, beta cells displayed GLUT2 expression comparable to uninfected diabetes-resistant controls. Immunostained insulin content of the beta cells also remained unchanged. Sections were also examined from Kilham Rat Virus inoculated diabetes-resistant rats with lymphocytic insulitis or diabetes. GLUT2 and insulin immunostaining were unchanged in non-diabetic rats with early insulitis. GLUT2 beta-cell staining was variably reduced in diabetic rats with established insulitis and reduced beta-cell insulin immunostaining. Hence, the initial stages of Kilham Rat Virus-induced diabetes in diabetes-resistant rats are not accompanied by a significant reduction in GLUT2 expression. These results suggest that the loss of GLUT2 does not play a significant role in the aetiology of diabetes in the Kilham Rat Virus-infected diabetes-resistant BB/Wor rat.

Animals↗
PubMedDate not supplied

Mineral status in selenium-deficient rats compared to selenium-sufficient rats fed vitamin-free casein-based or torula yeast-based diet.

To clarify the mineral status in selenium (Se)-deficient rats fed a vitamin-free casein (VFC)-based or torula yeast (TY)-based diet, 24 weanling male Wistar rats were divided into 4 groups fed diets using VFC or TY as the protein source and containing Se at sufficient (0.5 microgram/g, +Se) or deficient (0.019 microgram/g for VFC-based and < 0.005 microgram/g for TY-based diets, -Se) level for 8 wk. TY supplied a larger amount of extra minerals (Na, K, Ca, Mg, Fe, Mn, Zn, and Cu) except Se than VFC. Se concentration and glutathione peroxidase activity were significantly lower in TY-fed rats than in VFC-fed rats, as well as in -Se rats compared to +Se rats. Compared to +Se rats, Fe concentration was higher in liver and muscle of -Se rats fed the VFC-based diet and in plasma, heart, liver, and tibia of -Se rats fed the TY-based diet. Compared to +Se rats, decreases of Mn concentration appeared in plasma, heart, and tibia of VFC-fed -Se rats and in brain, heart, liver and tibia of TY-fed -Se rats. There was also a little imbalance in Ca, Mg, Na, K, and Cu caused by Se deficiency. The results indicated that Se deficiency induced the mineral imbalance in rats, especially an increase in Fe and decrease in Mn, which was more severe in TY-fed rats than VFC-fed rats. However, TY cannot be used as a model for both Se and other mineral deficiency because of the extra minerals except Se found in TY. Instead, VFC can be employed, which contains fewer minerals except Se than TY and also can produce a severe degree of Se deficiency.

Animals↗
PubMed1997

Rat lung phospholipid fatty acid composition in prepregnant, pregnant, and lactating rats: relationship to ozone-induced pulmonary toxicity.

Our laboratory has demonstrated recently that pulmonary inflammation induced by acute ozone exposure is much more severe in late stage pregnant and lactating rats than in postlactating rats or age-matched virgin females. It is currently widely believed that such pulmonary damage results, at least in part, from the reaction of ozone at sites of unsaturation in phospholipid fatty acid (PLFA) molecules located in the epithelial fluid layer lining the lung surfaces and/or the plasma membranes of epithelial cells underlying this fluid layer. The objective of this study was to compare the PLFA composition of lung tissue and surfactant from ozone-sensitive late stage pregnant and lactating rats with comparable tissue from relatively ozone-insensitive age-matched prepregnant (virgin female) rats to explore the possibility that changes in lung PLFA composition during pregnancy and/or lactation contribute to the enhanced sensitivity of these physiologic states to ozone. In addition, the correlation of changes in plasma PLFA composition with those in lung was investigated. There were minor differences in the composition of lung tissue and surfactant PLFAs between prepregnant rats and pregnant rats at day 17 of gestation and only slightly greater differences between prepregnant and lactating rats. Changes from the prepregnant state in the PLFA composition of lung tissue, but not surfactant, correlated with changes in the plasma only in lactating rats and not in pregnant rats. Overall, the double bond index of PLFAs in surfactant and lung tissue was decreased in pregnant and lactating rats compared with prepregnant rats. Thus, the increased sensitivity of pregnant and lactating rats to ozone-induced lung injury cannot be attributed to an increased availability of unsaturated fatty acids. In addition, the arachidonic acid composition of phospholipids did not appear to explain differences between prepregnant rats and pregnant or lactating rats in their inflammatory response to ozone. In conclusion, there is no evidence that the relatively minor changes in lung tissue PLFA composition which occur during pregnancy and lactation predispose rats in these physiologic states to ozone-induced pulmonary toxicity.

Animals↗
PubMed1991

Are the differential effects of chloral hydrate on hooded rats vs. albino rats due to pigmentation or strain differences?

Effects of chloral hydrate anesthesia on EEG power spectra and VEP components were examined as a function of both pigmentation and strain differences in rats. Ten albino Westenberg Long Evans rats (WLE A) were compared to ten pigmented Westenberg Long Evans rats (WLE P), and to ten Wistar albino (Wis A) rats. Albino rats required less chloral hydrate to reach a deep level of anesthesia than pigmented rats. Wistar rats remained anesthetized longer than WLE rats. During deep levels of anesthesia, the lowest EEG frequency band contained more power in Wistar rats than in WLE rats. During moderate levels of anesthesia, frequencies less than 4 Hz lost power while frequencies greater than 13 Hz gained across all rats. Wistar rats had more power in the frequencies less than 8 Hz than did WLE rats; pigmented rats had more power in the frequencies greater than 13 Hz than did albinos. VEP component latencies of pigmented rats were shorter than albinos. Component amplitudes were not significantly different between groups.

Anesthesia↗
PubMed2007

Binding of dimethylarsinous acid to cys-13alpha of rat hemoglobin is responsible for the retention of arsenic in rat blood.

The metabolism, disposition, and carcinogenicity of arsenic differ dramatically between humans and rats. To understand the molecular basis of these differences, we have characterized arsenic species in rats that were treated with inorganic arsenate (iAsV), monomethylarsonic acid (MMAV), or dimethylarsinic acid (DMAV) for up to 15 weeks. Arsenic significantly accumulated in the red blood cells (RBCs) of rats in the form of hemoglobin (Hb) complexed with dimethylarsinous acid (DMAIII), regardless of whether the rats were treated with iAsV, MMAV, or DMAV, suggesting rapid methylation of arsenic species followed by strong binding of DMAIII to rat Hb. The binding site for DMAIII was identified to be cysteine 13 in the alpha-chain of rat Hb with a stoichiometry of 1:1. Over 99% of the total arsenic (maximum 2.5-3.5 mM) in rat RBCs was bound to Hb for all rats examined (n = 138). In contrast, only 40-49% of the total arsenic (maximum approximately 10 muM) in rat plasma was bound to proteins. The ratios of the total arsenic in RBCs to that in plasma ranged from 88-423 for rats that were fed iAsV, 100-680 for rats that were fed MMAV, and 185-1393 for rats that were fed DMAV, when samples were obtained over the 15-week exposure duration. Previous studies have shown an increase in urothelial hyperplasia in rats fed DMAV. This is the first article reporting that treatment with iAsV in the drinking water also produces urothelial hyperplasia and at an even earlier time point than dietary DMAV. Dietary MMAV produced only a slight urothelial response. A correlation between the Hb-DMAIII complex and urothelial lesion severity in rats was observed. The lack of cysteine 13alpha in human Hb may be responsible for the shorter retention of arsenic in human blood. These differences in the disposition of arsenicals may contribute to the observed differences between humans and rats in susceptibility to arsenic carcinogenicity.

Amino Acid Sequence↗
PubMed1992

EDRF role in renal function and blood pressure of normal rats and rats with obstructive uropathy.

There is a decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) and an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) after release of bilateral ureteral obstruction (BUO) of 24 hours duration. The present studies examine the role of endothelium-derived relaxing factor (EDRF) in the renal hemodynamics of sham-operated rats (SOR) and rats in which BUO of 24 hours duration was unilaterally released. In both groups of rats, renal function and blood pressure were measured in the awake state under basal conditions and after administration of L-arginine (L-arg), the substrate for EDRF synthesis, followed by NwNAME, an L-arg antagonist, or after administration of NwNAME followed by L-arg. Administration of L-arg alone to SOR did not affect renal function, MAP or RVR. In SOR given L-arg and then NwNAME, there was significantly decreased GFR and ERPF and increased MAP and RVR. When NwNAME was given initially, similar changes were obtained, and these were reversed by the administration of L-arg. Rats given L-arginine immediately after unilateral release of BUO of 24 hours duration had significantly greater GFR and ERPF values and lower MAP and RVR than temporal controls. NwNAME given to BUO rats decreased renal function further and increased MAP and RVR. We found a dose-dependent increase in GFR and ERPF and a dose-dependent decrease in MAP and RVR in both SOR and rats with BUO given increasing amounts of L-arg. There was also a dose-dependent decrease in GFR and ERPF and an increase in MAP and RVR in SOR and rats with BUO given increasing amounts of NwNAME or NGNMA, the two different antagonists of L-arg. In another set of experiments, SOR and rats with BUO were given L-arg preoperatively (that is, 24 hr prior to study). Both groups of rats had significantly higher GFR and ERPF values and lower MAP and RVR than control rats. Sham-operated rats given NwNAME 24 hours prior to study had significantly lower GFR and ERPF and higher MAP and RVR than untreated rats. Rats with BUO given NwNAME prior to obstruction had no measurable renal function and had significantly higher values for MAP after release of obstruction. These studies confirm the role of L-arg administration, and presumably EDRF, in the regulation of MAP and renal function in sham-operated rats. The results of this study also suggest decreased availability of arginine for EDRF synthesis in rats with BUO.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Endothelin receptors mediating contraction of rat and human pulmonary resistance arteries: effect of chronic hypoxia in the rat.

1. We examined the endothelin (ET) receptors mediating contractions to ET-1, ET-3 and sarafotoxin S6c (SX6c) in rat pulmonary resistance arteries by use of peptide and non-peptide ET receptor antagonists. Changes induced by pulmonary hypertension were examined in the chronically hypoxic rat. The effect of the mixed ET(A)/ET(B) receptor antagonist SB 209670 on endothelin-mediated contraction was also examined in human pulmonary resistance arteries. 2. In rat vessels, the order of potency for the endothelin agonists was SX6c = ET-3 > ET-1 (pEC50 values in control rats: 9.12+/-0.10, 8.76+/-0.14 and 8.12+/-0.04, respectively). Maximum contractions induced by ET-3 and ET-1 were increased in vessels from chronically hypoxic rats. 3. The ET(A) receptor antagonist FR 139317 (1 microM) had no effect on the potency of ET-1 in any vessel studied but abolished the increased response to ET-1 in the chronically hypoxic vessels. The ET(A) receptor antagonist BMS 182874 (1 microM) increased the potency of ET-1 in control rat vessels without effecting potency in the pulmonary hypertensive rat vessels. 4. Bosentan (non-peptide mixed ET(A)/ET(B) receptor antagonist) increased the potency of ET-1 in control rat vessels but was without effect in the pulmonary hypertensive rat vessels. Bosentan (1 microM) inhibited responses to SX6c in control and chronically hypoxic rat vessels with pKb values of 5.84 and 6.11, respectively. The ET(B) receptor antagonist BQ-788 (1 microM) did not inhibit responses to ET-1 in any vessel tested but did inhibit responses to both SX6c and ET-3 (pKb values in control and chronically hypoxic rat vessels respectively: SX6c 7.15 and 7.22; ET-3: 6.68 and 6.89). BQ-788 (1 microM) added with BMS 182874 (10 microM) did not inhibit responses to ET-1 in control vessels but caused a significant inhibition of responses to ET-1 in chronically hypoxic preparations. 5. SB 209670 inhibited responses to ET-1 in both control and chronically hypoxic vessels with pKb values of 7.36 and 7.39, respectively. SB 209670 (0.1 and 1 microM) virtually abolished responses to ET-1 in the human pulmonary resistance artery. 6. In conclusion, in rat pulmonary resistance arteries, vasoconstrictions induced by ET-1, SX6c and ET-3 are mediated predominantly by activation of an ET(B)-like receptor. However, lack of effect of some antagonists on ET-1 induced vasoconstriction suggests that ET-1 stimulates an atypical ET(B) receptor. The increase in potency of ET-1 in the presence of some antagonists suggests the presence of an inhibitory ET(A)-like receptor. The influence of this is reduced, or absent, in the chronically hypoxic rats. Increased responses to ET-1 are observed in the chronically hypoxic rat and may be mediated by increased activation of ET(A) receptors. SB 209670 is unique in its potency against responses to ET-1 in both control and chronically hypoxic rats, as well as human, isolated pulmonary resistance arteries.

Animals↗