Various Strains Of Rats Research Articles

Levels of dopamine, 5-hydroxytryptamine and their metabolites in the striatum of rats of various strains receiving a high-calorie diet

The aim of this work was to study the effect of a high fat and carbohydrate diet (HFCD) and quercetin supplementation on the levels of dopamine (DA), serotonin (5-HT) and their metabolites in Wistar, DA transporter knockout (DAT-KO) and obese Zucker fa/fa rats. Animals received a control diet or HFCD for 62 days. Wistar and Zucker fa/fa rats received quercetin. The contents of DA, 5-HT, norepinephrine (NE), dioxyphenyl acetate (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolyl acetate (5-HIIA) in the striatum were determined by high-performance liquid chromatography (HPLC). DAT-KO homozygotes had lowered DA and increased HVA and DOPAC compared to Wistar rats. HFCD did not affect the content of NE and 5-HT. 5-HT was increased in DAT-KO homozygotes compared with Wistar receiving a control diet. 5-HIIA accumulated in larger amounts in DAT-KO compared to Wistar with the exception of those receiving quercetin with a control diet. Quercetin did not affect the levels of DA, 5-HT and their metabolites.

Tumor site concordance and genetic toxicology test correlations in NTP 2-year gavage, drinking water, dermal, and intraperitoneal injection studies

The National Toxicology Program has conducted 594, 2-year studies exposing various strains of rats and mice via different routes of exposure. In the current study, we analyze the results from 108 chemicals tested in 106, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via gavage. An additional 18, 2-year gavage studies have been conducted in Osborne–Mendel rats and B6C3F1 mice on 19 different chemicals. We analyze the results from 23 chemicals tested in 21, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via drinking water; 18 chemicals tested in 18, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via dermal application; and 11 chemicals tested in 11, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via intraperitoneal injection. The results from these 174 studies are analyzed and discussed separately. The neoplasticity of each chemical was analyzed for tumor incidence by species–sex category, tumor site concordance across species, and tumor site concordance across sex within species. When available the Ames Salmonella mutagenicity assay results, and any results from a test for genotoxicity other than the Ames test, were correlated with the neoplasticity results. Tumor site concordance across sex within species is generally higher than tumor site concordance across species. In addition, the high degree of variability of Ames test results suggests that historical Ames test data are less reliable than recent results conducted under good laboratory practices and employing Organization for Economic Cooperation and Development protocols relevant to the physicochemical characteristics of the test chemical.

Abstract P145: Renal Inflammation and Injury is Associated with Increased Lymphangiogenesis in Hypertension

Hypertension is associated with immune system activation and inflammation. Renal infiltration of both innate and adaptive immune cells contributes to injury, dysfunction, and increased blood pressure. Activated immune cells that exit blood vessels into the interstitium then travel through lymphatic vessels to draining lymph nodes where they signal to other immune cells to increase the immune response. It is unknown how renal lymphatic vessels change in the context of hypertension, immune system activation, inflammation, and injury. We hypothesized that renal macrophage infiltration, inflammation, and injury would significantly increase lymphangiogenesis in various strains of rats. SHR rats that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased numbers of renal lymphatic vessels at 40 weeks of age compared to WKY controls (total of 3 fields of view: 52 ± 1 vs. 28 ± 1; p<0.05). This was associated with increased renal macrophage infiltration. SHR rats that exhibit hypertension but minimal renal injury (SHR-B2 strain) had significantly less renal lymphatic vessel numbers compared to WKY controls (25 ± 2 vs. 28 ± 1; p<0.05) and normal levels of macrophages. The signals for lymphangiogenesis, VEGF-C and its receptor VEGF-R3, were both increased significantly at the protein level in the kidneys of SHR-A3 rats at 18 weeks but not different in the kidneys of SHR-B2 rats compared to WKY controls. To test whether the increased lymphangiogensis is due to hypertension and/or renal inflammation and injury, we obtained kidneys from Fischer 344 rats that exhibit normal blood pressure but develop renal inflammation and injury as they age. Compared to kidneys from control 4-month old Fischer rats, kidneys from 20-month and 24-month old Fischer rats had significantly increased numbers of lymphatic vessels (32 ± 3 vs. 74 ± 1 vs. 110 ± 6, respectively; p<0.05) and this was also associated with increased macrophage infiltration. Protein levels of VEGF-C and VEGF-R3 were increased significantly in 20-month old Fischer rats compared to 4-month old controls. These data together demonstrate that renal immune cell infiltration, inflammation, and injury increases lymphangiogenesis.

Strain Difference of Oxidative Metabolism of the Sedative-hypnotic Zaleplon by Aldehyde Oxidase and Cytochrome P450 In Vivo and In Vitro in Rats

The in vivo and in vitro metabolism of the sedative-hypnotic agent zaleplon (ZAL) to 5-hydroxylated ZAL (5-oxo-ZAL) and N-desethylated ZAL (desethyl-ZAL) was studied in four strains of rats. Incubation of ZAL with liver microsomes afforded desethyl-ZAL via cytochrome P450-catalyzed reaction, with little strain difference. In contrast, incubation of ZAL with liver cytosol afforded 5-oxo-ZAL with marked strain differences. ZAL hydroxylase activity was well correlated with aldehyde oxidase activity in these strains. The highest level of 5-oxo-ZAL and the highest activity of aldehyde oxidase were observed in cytosol from Sea:SD rats, followed by Jcl:SD rats, while Crj:SD and WKA/Sea rats showed low levels. When ZAL was administered to Sea:SD and WKA/Sea rats, both 5-oxo-ZAL and desethyl-ZAL were detected in blood as the major in vivo metabolites. However, the concentration of 5-oxo-ZAL was far higher in Sea:SD rats than in WKA/Sea rats, while that of desethyl-ZAL was far lower in Sea:SD rats. The levels of 5-oxo-ZAL in blood were closely correlated with the strain differences of cytosolic ZAL hydroxylase activity and benzaldehyde oxidase activity. Our results indicate that variability in the formation of 5-oxo-ZAL from ZAL in vivo in various strains of rats is primarily due to strain differences of hepatic aldehyde oxidase activity.

Protection of rat fetuses by quercetin against caffeine- induced cleft palate

Caffeine at high doses is a known rodent teratogen and it induces limb malformations along with cleft palate in various strains of rats and mice. The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, there are some evidence that quercetin is an antioxidant. Therefore, in this study, the prophylactic effect of quercetin on teratogenic effects of caffeine was evaluated. This study was performed on 26 pregnant rats that were divided into four groups. Control group received normal saline and test groups received caffeine (80 mg/kg), caffeine (80 mg/kg) plus quercetin (75 mg/kg), and quercetin (10 mg/kg), intraperitoneally at 9 to 11th days of gestation, respectively. Fetuses were collected at the 20th day of gestation and after determination of weight and length; they were stained by Alizarin red - Alcian blue method. Cleft palate incidence was 33.33% in fetuses of rats that received only caffeine and incidence was 1.49% in the group that received caffeine plus quercetin (75 mg/kg). The means of weight and length of fetuses from rat that received quercetin were significantly greater than those that received only caffeine. It is concluded that quercetin decreased cleft palate induced by caffeine, but this subject needs more detailed evaluation. Key words: Caffeine, quercetin, pregnancy, cleft palate, teratogenicity, fetus, rat.

The effects of caffeine and carvedilol on skeletal system of rat embryos in prenatal period

Caffeine at high doses is a known rodent teratogen and induces limb malformations along with cleft palate in various strains of rats and mice. The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, there are some evidence that carvedilol is antioxidant. Therefore, in this study, the prophylactic effect of carvedilol on teratogenic effects of caffeine was evaluated. This study was performed on 24 pregnant rats that were divided into four groups. Control group received normal saline and test groups received caffeine (80 mg/kg), caffeine (80 mg/kg) plus carvedilol (5 mg/kg) and carvedilol (5 mg/kg), intraperitoneally at 9 to 11th days of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and length, they were stained by Alizarin red - Alcian blue method. Cleft palate incidence was 33.33% in fetuses of rats that received only caffeine, while it was 2.85% in group which received caffeine plus carvedilol (5 mg/kg). The means of weight and length of fetuses from rats that received carvedilol were significantly greater than those that received only caffeine. It is concluded that carvedilol decreased cleft palate induced by caffeine, but this subject needs more detailed evaluation. Key words: Caffeine, carvedilol, gestation, cleft palate, teratogenicity, fetus, rat.

Factors Influencing Rat Survival in a Warm Renal Ischemia Model: Time to Adapt the Protocols

Introduction Survival in warm renal ischemia models is not only dependent on the treatment or surgical technique being evaluated, but also on factors inherent to the model itself. Use of rats of various strains in previous studies makes interstudy comparison difficult when trying to design an appropriate model control that would yield intermediate survival. In this study, impact of rat strain on survival after prolonged warm renal ischemia in the setting of delivery-controlled inhalational anesthesia was evaluated. Materials and methods Under general delivery-controlled inhalation anesthesia with isoflurane, Dahl salt-sensitive, Wistar-Furth, Sprague-Dawley, and spontaneously hypertensive rats (n = 66 rats) were subjected to 150 minutes of unilateral renal warm ischemia time, subsequent reperfusion, and contralateral nephrectomy. Animals were followed up for 1 month, after which survivors were euthanized and morphologic changes in kidneys were scored. Results Thirty-day survival was: Dahl salt sensitive, 78%; Wistar-Furth, 67%; Sprague-Dawley, 55%; and spontaneously hypertensive rats, 0% ( P < .0001). Histologic acute injury scores were higher for non-survivors versus 30-day survivors ( P < .0001). Conclusion Our data strongly suggest that rat strain is a major factor influencing survival and that strain and warm ischemia time selections must be considered together when designing a model control yielding intermediate survival. Further study is warranted in order to compare the effect of delivery-controlled inhalational versus historical anesthesia methods on animal survival.

Baseline serum cardiac troponin I concentrations in various strains of rats as determined with an ultrasensitive immunoassay

Baseline serum cardiac troponin I concentrations in various strains of rats as determined with an ultrasensitive immunoassay

Diazepam Metabolism in the Kidneys of Male and Female Rats of Various Strains

Previously, we have reported drastic strain differences of diazepam metabolism in the livers of a variety of rat strain. In this study, to characterize strain and sex differences of diazepam metabolism in the kidney, renal microsomal diazepam metabolic activities were determined in the Dark Agouti (DA), Sprague-Dawley (SD), Brown Norway (BN) and Wistar (WS) strains of rat. We found that the major pathway of diazepam metabolism in the kidney was diazepam N-demethylation, which is different from that in the liver, 3-hydroxylation. A Dose-course (12.5-200 muM of diazepam) study revealed that the DA and WS male rats had higher diazepam N-demethylation activity than the SD and BN rats. In contrast to the males, a lower activity of diazepam N-demethylation was observed in female BN rats. By Western blot analysis, constitutive protein expressions of cytochrome P450 (CYP) 2C11, which is responsible for diazepam N-demethylation, were detected in the 4 strain in both the male and female rats, and the BN rats had lower expression levels of CYP2C11 protein. However, we did not observe significant differences in the kinetic parameters of diazepam N-demethylation. Our results suggested that there was a strain difference in CYP-dependent diazepam N-demethylation in the rat kidney, which is different from the finding in liver microsomes.

Circadian Rhythm Regulations of the Cardiovascular System in Rats and Mice

The objective of this paper is to get more insight into the circadian regulation of the cardiovascular system, various strains of rats were studied as animal models of human primary and secondary hypertension. Experiments were performed under highly controlled environmental conditions under a light:dark (LD) schedule of 12 h 12 min. To test for the contribution of the biological clock(s), rats and mice were monitored under free-run conditions in total darkness (DD) as well as after a shift of the LD cycle simulating a westward jet-lag. The availability of implantable radiotelemetric devices made it possible to study various cardiovascular functions in freely moving, unrestrained animals. With the use of radiotelemetry, one can simulate the conditions in rodents (changing LD conditions, inducing light shifts) and finally study the effects of drugs, which might be helpful to ameliorate the symptoms.

IMPORTANCE OF CYP2D3 IN POLYMORPHISM OF DIAZEPAMP-HYDROXYLATION IN RATS

Diazepam was metabolized to three primary metabolites, 3-hydroxy-diazepam, N-desmethyl-diazepam, and p-hydroxy-diazepam. Our previous studies reported metabolic position-specific inter- or intrastrain differences in diazepam metabolism among Sprague-Dawley, Brown Norway, Dark Agouti, and Wistar rats. Especially, there were marked ( approximately 300 fold) inter- or intrastrain differences in diazepam p-hydroxylation activity at low concentration of substrate. In this study, we investigated the enzyme that catalyzes diazepam p-hydroxylation. The activity toward diazepam p-hydroxylation was inhibited by anti-cytochrome P450 2D (CYP2D) antibody, suggesting that this activity was catalyzed by CYP2D isoforms. Comparing the expression levels of the CYP2D subfamily in liver microsomes from various strains of rats using anti-CYP2D2 antibody, we found that there was a band of protein that was consistent with the phenotype of diazepam p-hydroxylation. N-terminal amino acid sequences of the specific protein exactly corresponded to those of CYP2D3, indicating that CYP2D3 might be involved in diazepam p-hydroxylation. Moreover, using rat CYP2D isoforms expressed in yeast, we tested CYP2Ds to catalyze diazepam p-hydroxylation. CYP2D1 and CYP2D2 practically did not participate in diazepam metabolism. On the other hand, diazepam p-hydroxylation was catalyzed by CYP2D3. CYP2D4 had high activity toward diazepam N-desmethylation, but not p-hydroxylation. In conclusion, the polymorphic expression of CYP2D3 caused the inter- or intrastrain differences in diazepam p-hydroxylation among rat strains or individuals.

Table of Content 5

Topiramate (TPM) is a novel neurotherapeutic agent currently indicated for the treatment of epilepsy and undergoing development for other central nervous system indications including neuropathic pain, bipolar disorder, and migraine prophylaxis. TPM is synthesized from d-fructose and contains a sulfamate moiety that is essential for its pharmacologic activity. TPM has been observed to significantly reduce body weight in patients treated for seizure, which has prompted the realization of preclinical studies to characterize the effects of TPM in the regulation of energy balance. Studies carried out in various strains of rats have provided good evidence for the ability of TPM to blunt energy deposition. Body composition analyses from rat trials have demonstrated that TPM inhibits fat deposition while reducing the activity of lipoprotein lipase (LPL) in various white adipose tissue depots. High doses of TPM (likely above the therapeutic dose range) have also been observed to reduce protein gain without catabolic effects. Although TPM cannot be described as a potent anorectic agent, it seems to have the ability to reduce food intake; significant reductions in food intake have been observed in female obese (fa/fa) Zucker rats and in female Wistar rats. TPM can also reduce energy deposition in the absence of alterations in food intake. This effect has been clearly emphasized in female lean (Fa/?) Zucker rats. In female Sprague–Dawley rats, TPM also increased energy expenditure and it has been observed to increase LPL activity in brown adipose tissue, which could indicate that TPM has the ability to enhance regulatory thermogenesis. In addition, TPM stimulates LPL activity in skeletal muscles, further emphasizing its potential to promote substrate oxidation. The mechanisms whereby TPM affects the regulation of energy balance have yet to be understood. TPM represents an antiepileptic drug (AED) with complex biochemical/pharmacologic actions. Its negative effects on energy deposition cannot be readily predicted from these actions, as AEDs are generally expected to stimulate body weight gain. Recent data, obtained from investigations aimed at assessing the effects of TPM on neuropeptidergic systems involved in the regulation of energy balance, have failed to demonstrate any significant effects of TPM on the neuropeptide Y and proopiomelanocortin systems. In conclusion, it is clear that TPM can reduce fat deposition by either reducing food intake or stimulating energy expenditure. The mechanisms whereby an AED such as TPM controls food intake and energy expenditure remains to be delineated.©1999 ASCRS and ESCRS

Contrasting circadian rhythms of blood pressure among inbred rat strains

The non-dipper pattern, i.e. the lack of nocturnal blood pressure (BP) fall, carries a high risk of cardiovascular complications, both in hypertensive and normotensive subjects. Without genetic engineering, experimental demonstration of the non-dipper phenomenon is lacking. The purpose of this study was to assess the haemodynamic and behavioural daily parameters among various strains of rats - spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) and Fischer 344 (F344) - in order to characterize their circadian patterns and to detect a non-dipper animal model. Changes in BP, heart rate (HR), and spontaneous locomotor activity (SLA) were recorded continuously for 11 days using telemetry in freely moving 10-week-old male SHR, WKY and F344 rats, in standardized laboratory conditions. Variations in haemodynamic and behavioural parameters were assessed in terms of day/night differences and spectral power corresponding with the 24-h period. All rats exhibited clear circadian variations in HR and in SLA, in synchrony with the light cycle. Light/dark differences in BP were significantly lower in F344 compared with those of SHR and WKY. The smaller circadian changes in BP observed in F344 were also demonstrated using spectral analysis: the peak detected at 24-h was reduced in F344 compared with SHR and WKY. The inbred F344 strain lacks the typical circadian BP rhythm while oscillations of HR and SLA are maintained, suggesting different regulatory mechanisms. The F344 strain may represent a useful animal model for studying the effects of drugs aimed at restoring the dipper status.

Folliculostellate cells determine the susceptibility of lactotropes to estradiol's mitogenic action.

Estradiol is known to increase lactotropic cell proliferation, but estradiol susceptibility varies among human populations and among various strains of rats. We had reported that folliculostellate (FS) cells regulate estradiol's mitogenic action on lactotropes; therefore, we studied their role in determining the susceptibility to estradiol in a high estradiol-responsive rat strain, Fischer 344 (F344), and in a low-responsive strain, Sprague Dawley (SD). Determination of total S-100-positive FS cells in the pituitary revealed that F344 rats have significantly more FS cells than do SD rats. Estradiol treatment did not change the number of FS cells in both F344 and SD rats. When cotransplanted with F344 pituitaries under the kidney capsule or cocultured with F344-derived lactotropes in vitro, FS cells derived from F344 rats increased estradiol's mitogenic action. They also increased estradiol's mitogenic action on SD-derived lactotropes in primary cultures. However, SD-derived FS cells failed to increase estrogen's action on F344- or SD-derived lactotropes. The levels of basic fibroblast growth factor production and secretion by TGF-beta 3 and estradiol were much higher in F344-derived FS cells than in SD-derived FS cells. However, the lactotropes' growth response to basic fibroblast growth factor was similar in both strains. These data suggest that cell-cell interaction between FS cells and lactotropes regulates estradiol's mitogenic action on lactotropes and also determines lactotrope susceptibility to the steroid.

Regulation mode of evaporative cooling underlying a strategy of the heat-tolerant FOK rat for enduring ambient heat.

Compared with other rat strains, the inbred FOK rat is extremely heat tolerant. This increased heat tolerance is due largely to the animal's enhanced saliva spreading abilities. The aims of the present study were to 1) quantify the heat tolerance capacity of FOK rats and 2) determine the regulatory mode of the enhanced salivary cooling in these animals. Various strains of rats were acutely exposed to heat. In the heat-intolerant strains, saliva spreading was insufficient and the core temperature (Tc) rose rapidly. In contrast, FOK rats maintained an elevated Tc plateau (39.5 +/- 0.7 degrees C) for 5-6 h over a wide range of ambient temperatures (Ta) (37.5-42.5 degrees C). In hot environments the FOK rats secreted copious amounts of saliva and spread it over more than the entire ventral body surface. FOK rats had a low Tc threshold for salivation, and the salivation rate increased linearly in proportion to the Tc deviation from the threshold. No strain difference or temperature effect was observed in the saliva secretion rate from in vitro submandibular glands perfused by sufficient doses of ACh. These results suggest that 1) the ability of FOK rats to maintain a moderate steady-state hyperthermia (39.5 +/- 0.7 degrees C) over a wide Ta range is enabled by a lowered threshold Tc for salivation and functional negative-feedback control of saliva secretion and 2) strain differences in ability to endure heat stress are mainly attributable to changes in the thermoregulatory control system rather than altered secretory abilities of the salivary glands.

Use of PVC Conduits by Rats of Various Strains and Ages Housed Singly and in Pairs

This study observed the frequency with which laboratory rats (Rattus norvegicus) entered polyvinylchloride (PVC) conduits placed in their cages to provide environmental enrichment. The study found that use of PVC conduits by Norway rats varied with subjects' strain, age, sex, and housing condition. Adult male Long-Evans rats rarely entered PVC conduits unless housed in pairs, in which case the lighter (presumably subordinate) pair member frequently used the conduit, possibly to avoid contact with his dominant partner. Adult male Sprague-Dawley rats entered PVC conduits only during the illuminated portion of the day-night cycle and only if housed on shelves exposed to direct overhead illumination. Both juvenile rats and female rats made extensive use of PVC conduits throughout the day-night cycle. This article discusses implications of these findings for determining how best to enrich environments in which laboratory rodents are maintained.

Spontaneous spike-wave discharges in rat neocortex and their relation to behaviour

A certain proportion of laboratory rats of various strains show spontaneous nonconvulsive ECoG seizures in the form of bursts of spike-and-wave discharges (SWD). Since in the majority of behavioural experiments the EEG is not controlled, the experimenter is usually unaware of this fact. The purpose of the present work was to find out whether the SWD trait is related to the rats behavioural performance in selected test situations. The experiment was performed on two groups of male Wistar rats, outbreds, aged six (group 6M, n = 17) and 24 months (group 24M, n = 14). First, in both groups the following forms of behaviour were assessed: (1) seeking water reward in an 8-arm radial maze, (2) exploration of a new object, (3) inhibition of a locomotor response (passive avoidance), and (4) paw-lick response to a thermal stimulus (54.5°C) applied to the feet before and after intermittent footshock. The rats were then implanted with intrabrain electrodes and the level of SWD activity was assessed. Rats of the 24M group, compared with those of the 6M one, showed a significantly shorter exploratory response to a new object and diminished responsiveness to heat. The groups did not differ, however, in passive avoidance and radial maze performance. The analysis of 3-h ECoG sections revealed SWD bursts in 73% and nearly 93% of rats from groups 6M and 24M, respectively. The groups did not differ in the number of bursts or in the total duration of SWD activity. A correlation analysis of pooled data from both groups revealed that the exploration time of a new object was significantly (negatively) correlated with the number of SWD episodes. The total duration of SWD activity, and the number of perseveration errors in the radial maze, was significantly (positively) correlated with the total duration of SWD activity. The results suggest that SWD rats are behaviourally impaired in some test situations.

Precision of measurement of tissue concentrations by RLG.

Existing investigations about the precision of radioluminography (RLG) are restricted to descriptive analysis of the tissue samples. The aim of the present experiments was to obtain a general prospective statement about the precision that the RLG method can achieve. Several pharmaceutical companies in Europe participated in the experiments. Albino rats of various strains were dosed with various (14)C-labeled compounds. Whole-body sections were produced, and blood calibration scales were set up with standard radioactivity sources of dog or rat blood. Photostimulated luminescence was detected using Fuji imaging plate BAS-III. For each organ separately, variability was investigated on each of the levels: rat, section of rat, region within section, and residual, with the help of variance components. The producing company was seen as a fixed factor and adjusted for. A mixed linear model was fitted to the log-transformed data. The variance component (SD estimate) for the residual term gave the desired prospective statement about the achievable precision of the RLG method. Exponential back transformation from the logarithmic to the natural scale transformed the SD estimates to multiplication factors. In total, 29 organs were investigated. The RLG method was comparable in precision to the dissection/combustion method.

Strain difference in rats with experimental giant cell myocarditis.

Immunogenetic mechanisms may be involved in the pathogenesis of myocarditis and dilated cardiomyopathy. The present study investigated the incidence, histopathology and histocompatibility characteristics of experimental giant cell myocarditis in various strains of rats. Experimental giant cell myocarditis was induced by immunization with porcine cardiac myosin in Lewis (RT-1(l)), Dahl (DIR/Eis) (RT-1(l)), Fisher (RT-1(lv 1)) rats, but not in Dahl (DIS/Eis) (RT-1(l)) or Brown Norway (RT-1(n)). Myocarditis was most severe in the Lewis rats and their heart weight/body weight ratio was significantly higher than that of control rats immunized with Freund's complete adjuvant alone. In conclusion, this study provides evidence that the expression and severity of experimental giant cell myocarditis may be determined mainly by genetic factors, including both major histocompatibility complex genes as well as other genes, which may be controlled by an immune mechanism.

Effects of angiotensin II and IV on geniculate activity in nontransgenic and transgenic rats

Microiontophoretic ejection of angiotensin II and angiotensin IV in the vicinity of geniculate neurons was used to study the effects of these peptides on the discharge rate and the discharge pattern of extracellularly recorded activity. The main aim of the experiments was to study the effects of angiotensins in different strains of rats anesthetized with urethane (normotensive Wistar, normotensive Sprague–Dawley and hypertensive, transgenic (TGR(mREN2)27) rats). Both angiotensins mostly increased the spontaneous activity of angiotensin-sensitive geniculate neurons in all strains. Angiotensin II reduced the number of bursts in most neurons, whereas angiotensin IV significantly enhanced it. Inhibitory effects of angiotensins on spontaneous as well as on light-evoked activity could be effectively blocked by GABA A or GABA B receptor antagonists. Therefore, it can be supposed that angiotensin-containing afferent fibers innervate both projection and local circuit neurons of the dorsal lateral geniculate nucleus. In addition, angiotensin II suppressed excitation induced by glutamate receptor agonists in most neurons tested. Angiotensin-induced effects could be blocked by specific receptor antagonists. There were no significant differences in the effects of angiotensins in the various strains of rats, except for the latencies of the neuronal responses to the iontophoretic ejection of angiotensins.