The effect of pentacaine on different models of gastric and duodenal damage and on gastric acid secretion was studied after oral and parenteral administration. A proportional involvement of local and systemic effects of pentacaine was found in phenylbutazone-induced and cold-restraint stress-induced lesions, whereas in ethanol- induced lesions oral administration was the only effective way. On the other hand, duodenal lesions and gastric acid secretion were substantially affected by parenteral administration. The possible mechanisms involved in these differences are discussed.
In in vivo cardiovascular or toxicological studies involving rat models, changes in selected electrocardiographic (ECG) parameters are monitored after various interventions to assess the origin and development of heart rhythm disorders. Each ECG parameter has diagnostic significance; as such, commonly evaluated ECG parameters, including heart rate, PR interval, P wave duration, P wave amplitude, QRS complex, QT and QTc interval duration, R wave and T wave amplitude, of rats under various types of general anesthesia were the focus of this study. Studies that performed in vivo cardiovascular or toxicological experiments in rats were retrieved from a search of the Web of Science database for articles published mainly between 2000 and 2021. In total, the search retrieved 123 articles. ECG parameters that were reported as baseline or control values were summarized and averages with ranges were calculated. It is important to be cautious when interpreting results and, in discussions addressing the mechanisms underlying a given type of arrhythmia, acknowledge that initial ECG parameters may already be affected to some extent by the general anesthesia as well as by sex and the time of day the experiments were performed. and autoři: Pavol Svorc, Pavol Svorc Jr
Increased plasma cholesterol levels are listed between the major
atherosclerosis risk factors. The final plasma cholesterol levels
result from the interplay between the genetic and environmental
(diet, physical activity) factors. Little is known, how dietary
factors influence epigenetics. We have analyzed, if an overgeneration feeding of rat with cholesterol influences total liverDNA methylation, and if total liver-DNA methylation differ
between the different rat strains (Prague hereditary
hypercholesterolemic rats, Prague hereditary hypertriglyceridemic
rats and Wistar Kyoto rats). The animals were feed with high fat
(additional 5 % over normal capacity) high cholesterol (2 %) diet
for 14 days. DNA methylation in the liver tissue in different
generations was analyzed using the liquid chromatography
coupled with tandem mass spectrometry. We have not observed
any significant changes in total liver-DNA methylation over the
9 generations of animals feed by fat/cholesterol enriched diet.
Additionally, there were no differences in DNA methylation
between different rat strains. In animal model, the dietary
changes (hypercholesterolemic diet) not significantly influence
the total DNA methylation status within the liver.
The Prague Hereditary Hypercholesterolaemic (PHHC) rat is a strain of the Wistar rat very sensitive to dietary cholesterol.The dynamics of changes in serum and liver lipids and lecithin : cholesterol acyltransferase (LCAT) were studied immediatelly after the switch to a high cholesterol diet. Immediate cumulation of free and esterified cholesterol in the liver after the increase in alimentary cholesterol intake is supposed to be the regulating step leading to a subsequent increase in serum cholesterol concentration. Activity of LCAT was negatively correlated to the concentration of free cholesterol in the liver, very early after the cholesterol diet was introduced, a possibility of a down regulation of enzyme synthesis similarly to the regulation of synthesis of cholesterol in hepatocytes was observed.
a1_Chronic hypoxia causes pulmonary hypertension, the mechanism of which includes altered collagen metabolism in the pulmonary vascular wall. This chronic hypoxic pulmonary hypertension is gradually reversible upon reoxygenation. The return to air after the adjustment to chronic hypoxia resembles in some aspects a hyperoxic stimulus and we hypothesize that the changes of extracellular matrix proteins in peripheral pulmonary arteries may be similar. Therefore, we studied the exposure to moderate chronic hyperoxia (FiO2 = 0.35, 3 weeks) in rats and compared its effects on the rat pulmonary vasculature to the effects of recovery (3 weeks) from chronic hypoxia (FiO2 = 0.1, 3 weeks). Chronically hypoxic rats had pulmonary hypertension (Pap = 26±3 mm Hg, controls 16±1 mm Hg) and right ventricular hypertrophy. Pulmonary arterial blood pressure and right ventricle weight normalized after 3 weeks of recovery in air (Pap = 19±1 mm Hg). The rats exposed to moderate chronic hyperoxia also did not have pulmonary hypertension (Pap = 18±1 mm Hg, controls 17±1 mm Hg). Collagenous proteins isolated from the peripheral pulmonary arteries (100-300 mm) were studied using polyacrylamide gel electrophoresis. A dominant low molecular weight peptide (approx. 76 kD) was found in hypoxic rats. The proportion of this peptide decreases significantly in the course of recovery in air. In addition, another larger peptide doublet was found in rats recovering from chronic hypoxia. It was localized in polyacrylamide gels close to the zone of a2 chain of collagen type I. It was bound to anticollagen type I antibodies. An identically localized peptide was found in rats exposed to moderate chronic hyperoxia. The apparent molecular weight of this collagen fraction suggests that it is a product of collagen type I cleavage by a rodent-type interstitial collagenase (MMP-13)., a2_We conclude that chronic moderate hyperoxia and recovery from chronic hypoxia have a similar effect on collagenous proteins of the peripheral pulmonary arterial wall., J. Novotná, J. Bíbová, V. Hampl, Z. Deyl, J. Herget., and Obsahuje bibliografii
Antifreeze proteins are an effective additive for low-temperature preservation of solid organs. Here, we compared static hypothermic preservation with and without antifreeze glycoprotein (AFGP), followed by nonfreezing cryopreservation of rat hearts. The heart was surgically extracted and immersed in one of the cardioplegia solutions after cardiac arrest. Control rat hearts (n=6) were immersed in University of Wisconsin (UW) solution whereas AFGP-treated hearts (AFGP group) (n=6) were immersed in UW solution containing 500 μg/ml AFGP. After static hypothermic preservation, a Langendorff apparatus was used to reperfuse the coronary arteries with oxygenated Krebs-Henseleit solution. After 30, 60, 90, and 120 min, the heart rate (HR), coronary flow (CF), cardiac contractile force (max dP/dt), and cardiac diastolic force (min dP/dt) were measured. Tissue water content (TWC) and tissue adenosine triphosphate (ATP) levels in the reperfused preserved hearts were also assessed. All the parameters were compared between the control and AFGP groups. Compared with the control group, the AFGP group had significantly (p<0.05) higher values of the following parameters: HR at 60, 90, and 120 min; CF at all four time points; max dP/dt at 90 min; min dP/dt at 90 and 120 min; and tissue ATP levels at 120 min. TWC did not differ significantly between the groups. The higher HR, CF, max dP/dt, min dP/dt, and tissue ATP levels in the AFGP compared with those in control hearts suggested that AFGP conferred superior hemodynamic and metabolic functions. Thus, AFGP might be a useful additive for the static/nonfreezing hypothermic preservation of hearts.
This experiment tested the effects of an intracerebroventricular injection of prostaglandin E1 on the sympathetic activation and the thermogenic changes in rats with ibotenate lesions of the ventromedial hypothalamus. Under pentobarbital anesthesia, twelve Sprague-Dawley male rats were lesioned bilaterally in the ventromedial hypothalamus with an injection of ibotenic acid (30 nmol into each side). Sham lesions were carried out in other twelve control rats. After 48 h, all animals were anesthetized with ethyl-urethane. The firing rate of the sympathetic nerves innervating the interscapular brown adipose tissue and the colonic and interscapular brown adipose tissue temperatures were monitored before and after an intracerebroventricular injection of prostaglandin E1 (500 ng) or saline. Prostaglandin E1 induced an increase in the firing rate of sympathetic nerves and the colonic and interscapular brown adipose tissue temperatures. These effects were reduced by the ventromedial hypothalamic lesion. Since ibotenic acid destroys cell bodies, the findings indicate that neurons of the ventromedial hypothalamus play a considerable role in the control of sympathetic activation and the thermogenic changes during prostaglandin E1 hyperthermia., M. Monda, A. Sullo, V. De Luca, A. Viggiano., and Obsahuje bibliografii
Interspecies differences in glycosidation potential in mammalian tissues represent a factor contributing to ambiguity when endobiotic and/or xenobiotic metabolic pathways are extrapolated from animals to man. Using the TLC/autoradiographic technique, we conducted an in vitro investigation involving mouse, rat, monkey, as well as human liver and kidney microsomes to evaluate their glycoconjugation potential towards 3H-labeled, purine-derived selective inhibitors of cyclin-dependent kinases such as olomoucine, bohemine, roscovitine, 6-(2-hydroxybenzyl)amino-2-(1-hydroxymethyl-2-methylpropyl)amino-9-isopropylpurine (compound A-4), and 6-(3-hydroxybenzyl)amino-2-[(1(R/S)-hydroxymethyl)propyl]amino-9-isopropylpurine (compound A-5) as aglycones. Principally, this study confirmed the aliphatic hydroxyl group of olomoucine-type inhibitors as a relatively suitable target for glucuronide, glucoside, xyloside, galactoside, and/or N-acetylaminoglucoside conjugation. Of the tissues examined, only the mouse microsomes were able to perform glucosidation and galactosidation reactions with the aglycones. On the other hand, monkey microsomes were superior to the mouse microsomes in a variety of glucuronide conjugates produced with compounds A-4 and A-5., K. Červenková, M. Belejová, Z. Chmela, M. Rypka, D. Riegrová, K. Michnová, K. Michalíková, I. Šúrová, A. Brejcha, J. Hanuš, B. Černý, K. Fuksová, L. Havlíček, J. Veselý., and Obsahuje bibliografii
Angiogenesis is known to be triggered by various stimuli including hypertension. It was previously found that NO-deficient hypertension is accompanied by structural remodeling of the cardiac muscle and large coronary arteries. This study was aimed to examine the qualitative subcellular alterations of capillaries in the heart of the rats treated with L-NAME (40 mg/kg/day for 4 weeks). The results showed that long-lasting inhibition of NO production induced an apparent activation of fibroblast function. This was associated with enhancement of fibrozation as well as with the induction of angiogenesis. Accordingly, fibroblasts were frequently located in the vicinity of capillary pericytes, which was followed by their detachment and migration. Moreover, besides inactive or even injured capillaries, the other ones exhibited extensive proteosynthetic activity linked to capillary growth, proliferation and migration of endothelial cells. The results strongly indicate enhanced triggering of the angiogenesis in L-NAME-induced NO-deficient hypertension., Ľ. Okruhlicová, N. Tribulová, I. Bernátová, O. Pecháňová., and Obsahuje bibliografii
A cheap, simple and fast procedure of building an infusion swivel is described for both short- and long-term experiments in rats. To assemble the swivel, plastic laboratory syringe elements, needles and a three-way stopcock are used. The swivel avoids cannula-kinking and permits animals free movement inside the cage. In addition, the gadget presented is inexpensive enough to make it disposable. Further advantages of the self-made infusion swivel depend on its disposability, it is time-saving, simplifies blood sampling or administration of drugs and prevents contamination, when using radiolabelled products. The haemodynamics and metabolism of rats subjected to restraint stress or ether-anaesthetized rats significantly differ from those of conscious freely moving animals. Whereas restraint stress provoked a more pronounced increase of blood pressure and heart rate, ether anaesthesia induced a 19 % rise in serum glucose. Thus, the device described in this study provides more physiological experimental conditions.