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At least 343 records · Page 19Linked to original sources

PubMed1997

Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: evidence for loss of its satiety effect in VMH-lesioned rats.

To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH-lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH-lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single i.v. (1.0 mg/rat) or intracerebroventricular (2.0 micrograms/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH-lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.

Animals↗

PubMed1999

Effect of fatty acids on the permeation of melatonin across rat and pig skin in-vitro and on the transepidermal water loss in rats in-vivo.

Transdermal delivery of melatonin would be advantageous in the treatment of sleep disorders considering the short biological half-life of melatonin and its variable bioavailability via the oral route. This study looked at suitable penetration enhancers for the transdermal permeation of melatonin. The permeation of melatonin was enhanced by all saturated and unsaturated fatty acids across both rat and porcine skin. There was a parabolic relationship between the carbon chain length of saturated fatty acids and the enhancement of melatonin permeation across rat and porcine skin. For rat skin, the maximum flux was observed with undecanoic acid (45.33 microg cm(-2) h(-1)) which enhanced the flux of melatonin 8.6 times compared with the control, whereas lauric acid produced the maximum flux of melatonin (24.98 microg cm(-2) h(-1); 4-7 times) across porcine skin. An increase in the number of double bonds in cis-9-octadecanoic acid increased the flux of melatonin across rat skin. In contrast, with porcine skin, the flux of melatonin decreased as the number of double bonds increased, although the flux values were not statistically significant. Treatment of rats with undecanoic acid, oleic acid and linolenic acid for 3 h using Hill top chamber enhanced the transepidermal water loss significantly. The maximum transepidermal water loss was observed with undecanoic acid and linolenic acid among saturated and unsaturated fatty acids, respectively. Nonanoic acid and myristic acid did not cause a significant change in the transepidermal water loss. The enhancement effect of saturated fatty acids on the permeation of melatonin was dependent on the chain-length of the fatty acid in both rat and porcine skin. While an increase in the number of double bonds in the fatty acid increased the flux of melatonin in rat skin, no significant difference in the flux was observed with porcine skin. The permeation enhancement of melatonin by saturated and unsaturated fatty acids across rat skin was significantly higher than that of porcine skin. A positive correlation was observed between the permeation enhancement effect of the fatty acids across rat skin in-vitro and the transepidermal water loss in rats in-vivo, suggesting that there is a similarity in the mechanism by which fatty acids enhance the permeation of melatonin and in the enhancement of transepidermal water loss. We conclude that saturated fatty acids such as undecanoic acid or lauric acid which showed maximum permeation across rat and porcine skin, respectively, may be used as potential penetration enhancers in the development of a transdermal delivery system for melatonin.

Acids, Acyclic↗

PubMed1997

In vitro studies of the stimulation of insulin secretion and B-cell proliferation by rat placental lactogen-II during pregnancy in rats.

The present study investigated the effect of rat placental lactogen-II (rPL-II) on insulin secretion and B-cell proliferation of the maternal islets during the last half of pregnancy in rats using a homologous system. Pancreatic islets were isolated from nonpregnant rats and rats at day 13 of pregnancy and cultured for 8 days in medium containing trophoblast culture medium or purified hormones. The medium was changed daily and insulin concentrations were determined by measuring immunoreactivity. The number of proliferating B cells were determined by double staining for both insulin and 5'-bromo-2'-deoxyuridine (BrdU) incorporated into replicating DNA during the last 24 h of incubation. rPL-II-enriched medium, in which trophoblasts of placentae from rats at day 13 of pregnancy were incubated for 8 days, was added to the islet culture system. Insulin concentration in the medium of non-pregnant rat islets was significantly increased and doubled on incubation in 100% trophoblast culture medium. Addition of purified rPL-II to the culture medium of pregnant rat islets stimulated insulin secretion at the concentrations of 50-500 ng ml-1 in a dose-dependent manner. The stimulatory effect of rPL-II on insulin secretion was found to be more than double that with rat prolactin (rPRL) and rat growth hormone (rGH) at 100 ng ml-1. For determination of B-cell proliferation, non-pregnant rat islets were incubated with rPL-II, rPRL or rGH at 1000 ng ml-1 for 8 days and then 10 mmol BrdU l-1 was added during the last 24 h of incubation. rPL-II (5.30 +/- 0.36%), rPRL (3.79 +/- 0.34%) and rGH (2.87 +/- 0.29%) significantly increased the rate of incorporation of BrdU into the B cells compared with that of the control (1.34 +/- 0.18%). These results indicate that rPL-II directly regulates insulin secretion and B-cell proliferation of maternal islets during the last half of pregnancy in rats.

Animals↗

PubMed1991

Role of platelet-activating factor in renal function in normal rats and rats with bilateral ureteral obstruction.

Platelet-activating factor (PAF) is a powerful vasodilator with important effects on kidney function. It has been suggested that the renal effects of PAF are mediated by thromboxane A2 (TxA2). We examined the effect of PAF on renal function in sham-operated rats and rats that had undergone unilateral release of bilateral ureteral obstruction (BUO) of 24-hr duration, a condition in which the synthesis of TxA2 is increased. To eliminate systemic hemodynamic changes, PAF was infused directly into the left renal artery using the lowest dose that affected renal function (2.3 x 10(-13) moles/min). Infusion of PAF significantly decreased the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in normal rats and rats with BUO. Normal (sham-operated) rats pretreated with an inhibitor of TxA2 synthesis also had a significant decrease in GFR after administration of PAF (ERPF also decreased, but not significantly). Rats with BUO pretreated with an inhibitor of TxA2 synthesis had significantly greater basal GFR and ERPF (increases of 72 and 171%, respectively) than untreated BUO rats. Administration of PAF to the former group further increased GFR and ERPF (by 37 and 39%, respectively; P less than 0.001). The role of endogenous PAF was evaluated by administering a specific PAF receptor antagonist. Sham-operated rats pretreated with high doses of the PAF receptor antagonist had significantly higher mean arterial pressure values than normal untreated rats, and had no decrease in GFR and ERPF during PAF infusion. Rats with BUO pretreated with the PAF antagonist had a significant, dose-dependent decrease in basal GFR and ERPF. These data suggest that endogenous PAF has a vasodilatory role in obstructive nephropathy. No significant differences in eicosanoid excretion in the urine corrected per GFR were observed during infusion of PAF in any of the groups examined. In BUO rats with intact TxA2 synthesis, exogenous administration of PAF decreased renal function, presumably through further increases in the production of TxA2. However, when TxA2 production was inhibited, PAF administration increased GFR and ERPF, presumably due to its unopposed vasodilatory properties. The data suggest an important role of PAF in the hemodynamic changes seen in obstructive nephropathy.

Animals↗

PubMed1999

Serotonergic neuronal activity in the dorsal raphe nucleus of selectively bred alcohol-preferring and alcohol-nonpreferring rats and unselected wistar rats.

BACKGROUND: Selectively-bred alcohol-preferring (P) rats have fewer serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) than do alcohol-nonpreferring (NP) rats. The present study was designed to test the hypothesis that the remaining 5-HT neurons in P rats compensated for their reduced number by increasing neuronal activity. METHODS: Spontaneous activity was recorded from single-spiking and bursting 5-HT neurons in the DRN of unanesthetized paralyzed, alcohol-naive P, NP, and Wistar rats. Firing frequencies, the percentages of action potentials in bursts, and the percentages of bursting neurons were evaluated. RESULTS: There were no significant differences among the three groups of rats in any of the parameters measured. Power analyses were performed on preliminary data to determine the sample sizes necessary for detection of significant differences. The mean firing frequencies of single-spiking 5-HT neurons averaged 1.8 (37 neurons), 1.7 (17 neurons), and 1.8 (41 neurons) spikes per second in P, NP, and Wistar rats, respectively. For bursting 5-HT neurons, the percentages of action potentials in bursts for P, NP, and Wistar rats were 55.0% (24 neurons), 49.7% (18 neurons), and 55.1% (21 neurons). The mean percentages of bursting 5-HT neurons encountered per electrode penetration were 44% for P rats (n = 28), 44% for NP rats (n = 14), and 34% for Wistar rats (n = 26). CONCLUSIONS: The results indicate that the sample of 5-HT neurons recorded in the DRN of P rats had not compensated for a reduced number by altering neuronal activity.

Action Potentials↗

PubMed2004

Bone loss in regucalcin transgenic rats: enhancement of osteoclastic cell formation from bone marrow of rats with increasing age.

Bone loss was previously shown to be induced in the femoral tissue of regucalcin transgenic (TG) rats. Regucalcin is expressed in rat bone marrow cells and its expression is enhanced in regucalcin TG rats. This study was undertaken to determine the change in osteoclastic bone resorption in regucalcin TG rats with increasing age. Femoral-diaphyseal and -metaphyseal tissues were obtained from normal (wild-type) and regucalcin TG rats aged 5, 14, 25 or 50 weeks. Calcium content in the femoral-diaphyseal and -metaphyseal tissues was significantly decreased in regucalcin TG male and female rats aged 5, 14, 25 or 50 weeks as compared with the value obtained from normal rats with each age. When the marrow cells obtained from normal or regucalcin TG rats were cultured for 7 days, the number of tartrate-resistant acid phosphatase (TRACP), a marker of osteoclasts, positive multinucleated cells (MNCs) were significantly increased in the marrow culture of regucalcin TG male and female rats aged 5, 14, 25 or 50 weeks. The effect of parathyroid hormone [human PTH (1-34); 10(-7) M] or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-7) M] in stimulating TRACP-positive MNC formation was significantly enhanced in regucalcin TG male and female rats aged 14 or 25 weeks. This study demonstrates that osteoclastic bone resorption is stimulated in regucalcin TG male and female rats with increasing age.

Acid Phosphatase↗

PubMed2002

[A pilot study of bone marrow stromal cells intraocular transplantation in the S334 transgenic rats and Sprague-Dawley rats].

PURPOSE: To investigate the survival and differentiation of human bone marrow stromal cells (BMSC) intraocular transplantation in newborn S334 retinal degeneration transgenic rats and (Sprague-Dawley)SD rats. METHODS: Human bone marrow stromal cells line was grown on the adhesive substrate in the condition media including a-Modified Eagle medium (a-MEM)/10% fetal bovine serum. The experiments were divided into four groups: Group 1: BMSC + (Retinoid Acid) RA transplanted in S334 transgenic rats (n = 5); Group 2: BMSC transplanted in S334 transgenic rats (n = 5); Group 3: BMSC + RA transplanted in SD rats (n = 5); Group 4: BMSC transplanted in SD rats (n = 5). 2 microl cell suspension (about 4 x 10(4) cells) was injected into the vitreous space in the transgenic rats and normal SD rats at Postnatal 1 (P1) respectively. The right eyes were treated eyes and the left eyes were used as control. At P14 and P23, the rats were killed and enucleated for histological assays using plastic section. RESULTS: In Group 1, the transplanted cells were well survived. They could continue to differentiate and participate in late-stage retinal development. The number of inner nuclear layer increased. Moreover, the host retina increased their thickness, but photoreceptor cells were not rescued from transplant. In Group 2, at P14, the BMSC continue to differentiate toward their linage cell fate and formed into hemorrhage island structures with few neurons if RA was not applied. Group 3, BMSC could survive, migrate. The number of inner nuclear layer increased also. In Group 4, it revealed that host retina structures were disorganized and transplant cells formed atypical proliferating mass. CONCLUSIONS: This pilot experiment indicated that bone marrow stromal cells could survival, differentiate and participate in the retinal development after transplanted into vitreous space in the new born transgenic rats and SD rats. Histological assays showed that transplanted cells integrated with inner nuclear layer of host retina. Thus, bone marrow stromal cells may be a useful vehicle for auto- transplantation for the therapy of variety of retinal degenerative disorders.

Animals↗

PubMed1992

Collagen-induced arthritis in rats. Examination of the epitope specificities of circulating and cartilage-bound antibodies produced by outbred and inbred rats using cyanogen bromide-derived peptides purified from heterologous and homologous type II collagens.

To determine the number and location of antibody binding epitopes on type II collagen, outbred and inbred rats were immunized with chick, bovine, human, and rat type II collagen (CII, BII, HII, and RII); all sera were assayed for reaction with a panel of CB peptides purified and renatured from the immunizing collagen and from RII. Antibody reaction patterns (profiles) varied among individual outbred rats but were essentially constant over time and changed little after boosting. The strongest antibody reactions were to CB11, CB9-7, and CB12 followed by CB8, CB10, and CB6. Antibody profiles varied depending on the species of collagen used for immunization and the strain of rat immunized. Except for CB10, where antibodies were largely specific for heterologous collagens, antibodies reactive with all other CB peptides cross-reacted strongly with renatured rat CB peptides. Sera from inbred BB rats immunized with BII, CII, or HII reacted best with CB11, unlike antisera to RII that reacted strongly with CB9-7. Inbred LEW, COP, WKY, F344, and BUF rats immunized with BII reacted strongest with CB9-7 and variably with CB11 and CB12. BBxLEW F1 hybrid rats reacted almost equally with CB11 and CB9-7 producing an antibody profile intermediate to those elicited in the parent strains. Finally, antibodies reactive with rat CB11, CB9-7, and CB12 could be eluted from normal rat cartilage incubated in anti-BII serum; antibody eluate profiles generally paralleled the profile produced by the sera applied to cartilage. Taken together, these findings indicate that multiple antibody-reactive epitopes on type II collagen may be instrumental in the initiation of collagen-induced arthritis in rats, particularly shared or cross-reactive epitopes located within CB11, CB9-7, CB12, and CB8.

Animals↗

PubMed1989

[A study of daunomycin rats--is it possible to use daunomycin rats as an experimental model of chronic renal failure?].

Daunomycin rats are frequently used as an experimental model of nephrotic syndrome. We accidentally left daunomycin rats for a long time, and after death, these rats showed extensive scarring of the kidney. Since then, we have been studying whether daunomycin rats can be used as an experimental model of chronic renal failure. Female Wistar rats were injected i.v. with a single dose of daunomycin 12 mg/kg or 6 mg/kg body wt. We then observed the rats for six months. The rats in the 12 mg/kg injection group died within three to six months. All rats died from chronic renal failure. The BUN and creatinine levels significantly increased from seven weeks after daunomycin 12 mg/kg injection. At the end stage, renal anemia and hyperphosphatemia were noticed. There was an inverse relationship between the life span of daunomycin rats and urine protein level at four weeks. Rats with a large amount of urine protein at four weeks died of uremia at an early age. We concluded that daunomycin rats can be used as an experimental model of chronic renal failure.

Animals↗

PubMed1994

Occurrence of islet cell reactive autoantibodies in diabetes-prone BB/OK rats is not associated with the onset of diabetes: a cross-sectional study of BB rats and their diabetes-resistant congenic strains.

Diabetes-prone BB rats are one of the extensively studied animal models of human type 1 (insulin-dependent) diabetes. We have detected islet cell reactive autoantibodies (ICRA) in sera of age-matched (120 days of age) diabetic and non-diabetic diabetes-prone BB/OK rats compared to sex- and age-matched diabetes-resistant LEW.1A control rats by cellular enzyme-linked immunosorbent assay (CELISA) using either desiccated or viable rat insulinoma (RIN) cells as target. The antibody levels measured using desiccated RIN cells (mean O.D. +/- SD; prevalence) of the diabetic group (1.41 +/- 0.59; 94.1%) and the non-diabetic group (1.23 +/- 0.48; 100%) were significantly (p < 0.01) increased compared to those of the diabetes-resistant LEW.1A control rats (0.24 +/- 0.1; 3.2%). Additionally, in a 209-day-old group of non-diabetic diabetes-prone BB/OK rats the autoantibody levels were further significantly (p < 0.01) increased (2.65 +/- 0.48; 100%). Comparing both congenic rat strains BB.1A/OK and LEW.1BB/OK, only the BB.1A/OK rats which bears the genetic background of diabetes-prone BB/OK rats were found to be antibody positive (0.68 +/- 0.43; 63.1%). The results were confirmed by the CELISA using viable RIN cells. We conclude that the prevalence of islet cell autoantibodies in diabetes-prone BB/OK rats and congenic BB.1A/OK rats is closely associated with the genetic susceptibility to diabetes and may be independent of Beta-cell destruction, but they are not a predictive marker for the onset of the disease in this animal model.

Aging↗

PubMed1997

Models of HTLV-I-induced diseases. Infectious transmission of HTLV-I in inbred rats and HTVL-I env-pX transgenic rats.

To examine the pathogenic roles of HTLV-I in HTLV-I-induced diseases, we developed two models; namely HTLV-I carrier rats and HTLV-I env-pX transgenic rats. Among life long HTLV-I carriers in seven rat strains, only WKAH rats with the RT1k haplotype developed chronic progressive myeloneuropathy, resembling HAM/TSP clinically and histologically in humans, designated as HAM rat disease and after long incubation periods. Apoptosis of myelin forming cells, oligodendrocytes and Schwann cells associated with HTLV-I infection appears to be the primary cause of HAM rat disease. Local activation of the pX gene and TNF alpha gene was evident in these rats. WKAH rats transgenic for HTLV-I env-pX gene were established and at age 5 weeks, swelling of the bilateral ankle joints began to develop and histological features of the affected joints resembled findings in cases of rheumatoid arthritis (RA): high-titers of rheumatoid factors were present in these rats. A series of vascular collagen diseases such as polyarteritis nodosa-like angiitis, polymyositis, myocarditis, and Sjögren's syndrome-like sialodenitis together with RA were present, even in one individual animal. These transgenic rats as well as HAM rats appear to be suitable animal models for elucidating pathogenic mechanisms implicated in HTLV-I-induced diseases and also various demyelinating vascular collagen diseases of unknown etiology.

Animals↗

PubMed1995

A rat model of HTLV-I infection: development of chronic progressive myeloneuropathy in seropositive WKAH rats and related apoptosis.

In seropositive HTLV-I carrier rats of the WKAH strain inoculated with 2 x 10(7) MT-2 cells at 3-6 months of age, chronic progressive myeloneuropathy, tentatively designated as HTLV-I-associated myelopathy (HAM) rat disease, occurred when the rats were 19-23 months old. Clinical and pathological findings were basically identical to those of seronegative HAM rats of the same strain neonatally inoculated with MT-2 cells. It appears that a high dose of MT-2 cells (10(8) cells) is more effective for the induction and acceleration of HAM rat disease. Seronegative and seropositive carriers of other strains (F344, ACI, and LEW), WKAH rats inoculated with HUT-78 (a human T cell line without HTLV-I infection), and untreated WKAH rats at comparable ages did not develop HAM rat disease, thereby indicating that development of this disease is caused by HTLV-I infection and is under strict genetic restriction of the host strain. Chronological examination of HAM rat disease induced by 10(7) MT-2 inoculation into newborn rats showed that the spinal cord lesion began to develop by 12 months of age. T cells were absent in the affected spinal cord throughout the disease process. There was morphological evidence of apoptotic death of oligodendrocytes in the affected spinal cord. Apoptosis was also confirmed by the specific nick end labeling of the nuclear fragmentation in situ, and the apoptotic oligodendrocytes confined to the demyelinating foci, and the number of apoptotic cells positively correlated with severity of the spinal cord lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Comparison of cardiovascular responses to intra-hippocampal mu, delta and kappa opioid agonists in spontaneously hypertensive rats and isolation-induced hypertensive rats.

OBJECTIVE: To investigate the cardiovascular effects of microinjection into the hippocampus of selective mu, delta and kappa opioid receptor agonists in anesthetized spontaneously hypertensive rats, isolation-induced hypertensive rats and their normotensive Wistar-Kyoto and group-housed Sprague-Dawley controls. METHODS AND RESULTS: The microinjection of a selective kappa agonist, spiradoline mesylate, (+/-)-(5alpha, 7alpha, 8beta)-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro++ +[4.5]dec-8-yl]-benzeneacetamide mesylate) (5 nmol) into the dorsal region of hippocampus, where injection of control saline failed to affect cardiovascular activities, induced centrally mediated decreases in mean blood pressure and heart rate in both hypertensive and normotensive rats. The effects were blocked by prior treatment of the hippocampus with nor-binaltorphimine dihydrochloride, a selective kappa opioid receptor antagonist The hypotensive and bradycardic effects were quantitatively similar between spontaneously hypertensive rats and Wistar-Kyoto rats and between isolated hypertensive rats and normotensive group-housed rats. The sequential administration of increasing doses (5, 10, 50 nmol) of the selective mu agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin and delta agonists [D-Ala2, D-Leu5]-enkephalin or [D-Pen2, D-Pen5]-enkephalin into the same areas of the hippocampus as used for the kappa agonist had no significant effects on mean blood pressure and heart rate in either hypertensive or normotensive rats. CONCLUSION: The present results extend our previous findings of a hippocampally mediated hypotensive effect of kappa agonists in the spontaneously hypertensive rat to the isolated rat model of hypertension and they establish that mu and delta opioid receptor agonists similarly applied are ineffective. Hippocampal kappa receptors may have a greater role in cardiovascular control than mu and delta receptors.

Analgesics↗

PubMed2002

Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell-mediated cytotoxicity.

Crry is a rodent membrane-bound inhibitor of complement activation and is a structural and functional analog of the human complement inhibitors decay-accelerating factor and membrane cofactor protein. We found previously that expression of rat Crry on a human tumor cell line enhances tumorigenicity in nude rats. In this study, we investigated the effect that rat Crry expressed on tumor cells has on rat cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The expression of rat Crry on the surface of different human tumor cell lines inhibited ADCC mediated by rat natural killer (NK) cells. C3 opsonization is known to enhance NK cell-mediated cytolysis, and a potential mechanism for Crry-mediated inhibition of NK cell lysis is through Crry modulation of C3 deposition on target cells. However, the transfection of tumor cell lines with Crry enhanced their resistance to NK cell-mediated lysis in the absence of exogenous complement. The resistance of Crry-expressing tumor cells to NK cell-mediated ADCC could be reversed by treatment with anti-Crry F(ab)(2). In addition, anti-Crry F(ab)(2) enhanced the susceptibility of 13762 rat mammary adenocarcinoma cells (that endogenously express Crry) to ADCC mediated by allogeneic rat NK cells in the absence of added complement. We found no evidence that rat NK cells were a source of complement for target cell deposition during the in vitro cytolysis assay. These data suggest a novel function for rat Crry in tumor immune surveillance that may be unrelated to complement inhibition.

Adenocarcinoma↗

PubMed1996

Effects of treatment of spontaneously hypertensive rats with the angiotensin-converting enzyme inhibitor trandolapril and the calcium antagonist verapamil on the sensitivity of glucose metabolism to insulin in rat soleus muscle in vitro.

We measured the sensitivity of glucose metabolism to insulin in soleus muscle preparations isolated from spontaneously hypertensive (SH) rats and normotensive age-matched Wistar-Kyoto (WKY) rats. SH rats were treated with the angiotensin-converting enzyme (ACE) inhibitor trandolapril (1 mg/kg) and/or a second antihypertensive drug, the calcium antagonist verapamil, alone (100 mg/kg) or as combination therapy (50 mg/kg). Treatment of SH rats with trandolapril or trandolapril in combination with verapamil for 6 weeks normalized the blood pressure. The estimated concentration of insulin required for half-maximal stimulation of glycogen synthesis (i.e., EC50 values) was approximately 500 microU/ml for muscles from both WKY and SH rats. This value is five times higher than the value obtained from soleus muscle preparations isolated from insulin-sensitive Wistar rats. This indicates that glycogen synthesis is insensitive to insulin in SH and WKY rat soleus muscle. Treatment of SH rats with trandolapril with or without verapamil improved the sensitivity of glycogen synthesis to insulin in soleus muscle. Further experiments investigated whether acute exposure (1 h) of insulin-sensitive skeletal muscle with either trandolaprilat (the active metabolite of trandolapril) or bradykinin (levels of which may be raised by ACE inhibition) could affect the insulin-stimulated rate of glucose metabolism. These results show that both trandolaprilat and bradykinin caused a small but significant increase in the rates of glucose metabolism. In conclusion, 1) SH and WKY rat skeletal muscle was insulin resistant, 2) chronic treatment of SH rats with trandolapril with or without verapamil normalized blood pressure and improved the response of glycogen metabolism to insulin, and 3) bradykinin and trandolaprilat acutely caused a small but significant increase in the rate of glycogen synthesis to a submaximal physiological concentration of insulin.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1984

Effects of Kilham rat virus on natural killer cell-mediated cytotoxicity in brown Norway and Wistar Furth rats.

Effects of Kilham rat virus (KRV) on selected aspects of the immune response of 2 strains of laboratory rats were studied. The Brown Norway rat and Wistar Furth rat were infected with KRV and serum antibody and interferon values and cytotoxic activity of natural killer cells were determined to assess the virus' effect on the rat's immune systems. Antibody values to the virus were increased in both strains after viral inoculation, and total antibody values were comparable in the 2 rat strains. Natural cytotoxicity was increased in Brown Norway rats 3 to 4 days after inoculation in contrast to a distinct depression for a period of 10 days in the Wistar Furth strain. Serum interferon was not measurable in either strain of rat. Seemingly, there is a distinct immune response to KRV in each rat strain and the cytotoxic activity response differs in these 2 strains of rats.

Animals↗

PubMed1997

Pharmacokinetics of DA-125, a new anthracycline, after intravenous administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.

Pharmacokinetic parameters-including tissue distribution, biliary excretion, and urinary excretion of M1-M4-were compared after an intravenous administration of DA-125 (a new anthracycline derivative; 20 mg/kg body weight) to male spontaneously hypersensitive rats (SHRs) at 16 weeks (an animal model for human primary hypertension) and at 6 weeks (corresponding to the early phase of the development of hypertension, at which time blood pressure remains within the normotensive range) of age and their age-matched control Kyoto-Wistar rats, and male deoxycorticosterone acetate-salt-induced Sprague-Dawley rats (DOCA-salt rats, an animal model for human secondary hypertension) at 16 weeks of age and their age-matched control Sprague-Dawley rats. Mean plasma concentrations of both M2 and M4, and the resultant area under the plasma concentration-time curve from time 0 to last measured time [AUCT; M2 (68.9 vs. 29.3 micrograms-min/ml) and M4 (53.4 vs. 33.4 micrograms-min/ml)], increased significantly in SHRs at 16 weeks of age, compared with their control rats. Similar results were also obtained from DOCA-salt rats at 16 weeks of age, compared with their control rats. However, values were not significantly different between SHRs at 6 weeks of age and their control rats. Previous data indicated that the significant increase in plasma concentrations and the resultant AUCT values of both M2 and M4 in SHRs at 16 weeks of age were due to the hypertension state itself, and not to any hereditary characteristics of the SHRs. The significantly increased plasma concentrations and the resultant AUCT values of M2 in both SHRs and DOCA-salt rats at 16 weeks of age were due to the significantly decreased biliary excretion of M2 and possibly to the increased amount of aldo-keto reductase in the liver. However, the increase in the two aforementioned pharmacokinetic parameters in the case of M4 were possibly due solely to the increased amount of aldo-keto reductase in the liver.

Age Factors↗

PubMed1996

Increased expression of schwannoma-derived growth factor (SDGF) mRNA in rat tumor cells: involvement of SDGF in the growth promotion of rat gliomas.

Schwannoma-derived growth factor (SDGF) is a member of the epidermal growth factor (EGF) family, having mitogenic activity on rat astrocytes, fibroblasts and Schwann cells. The SDGF gene is significantly expressed in the newborn rat lung and in the adult rat sciatic nerve. However, except for one rat schwannoma cell line, from which SDGF and its cDNA were isolated, nothing is known about SDGF expression in established tumor cell lines. We examined the expression level of the SDGF gene in a variety of rat tumor cell lines by Northern blotting and found that it was increased in 11 of 25 established lines. The most abundant SDGF mRNA, which was about 50-fold higher than in the newborn rat lung, was expressed in rat liver adenoma dRLa74 cells. In rat glioma cell lines, such as C6, 9L and T9, and in the rat hepatoma dRLh84 and H411E cells, the SDGF expression level was about 10-fold higher than in the newborn rat lung. In 8 of 13 cell lines expressing SDGF mRNA, the EGF receptor (EGFR) gene, the product of which is regarded as a functional receptor of SDGF, was co-expressed. In addition, transfected gene-dependent anti-sense SDGF RNA expression under the control of the human metallothionein promoter significantly suppressed the in vitro growth as well as in vivo tumorigenicity of 9L glioma cells. Our results suggest that SDGF acts as an autocrine growth factor in the development and growth of rat tumors such as gliomas.

Amphiregulin↗