The responsiveness of isolated high-pressure (aorta, renal artery) and low-pressure vessels (pulmonary artery) was compared during systemic hypertension induced by chronic inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME) in rats. L-NAME (40 mg/kg/day) was given to animals in their drinking water. After 4 weeks of L-NAME treatment, systolic blood pressure increased by 37 % as compared with that in the control group. Chronic L-NAME treatment resulted in significant reduction of endothelium-dependent relaxation to acetylcholine (10-8 to 3xl0-6 mol/1) in both types of vessels. The reduced relaxation was not influenced by acute pretreatment with indomethacin (10"5 mol/1), however, it was further reduced by acute pretreatment with additional L-NAME (10-4 mol/1). L-arginine (10-4 mol/1) improved the reduced relaxation. Endothelium- independent relaxation to sodium nitroprusside (10-9 to 10-6 mol/1) was unaffected by L-NAME treatment. /3-adrenoceptor-mediated relaxation to isoprénaline (10“8 to 3xl0-6 mol/1) was also not influenced by chronic L-NAME treatment Similar alterations in the responsiveness of high- and low- pressure vessels indicate rather the decisive role of nitric oxide restriction than that of elevated blood pressure in their development
We have investigated slow inactivation in a rat axonal K+ channel, the I channel. Using voltage steps to potentials between -70 mV and +80 mV, from a holding potential of -100 mV, we observed a marked slowing of inactivation at positive potentials: the time constant was 4.5±0.4 s at -40 mV (mean ± S.E.M.), increasing to 14.7±2.0 s at +40 mV. Slowed inactivation at positive potentials is not consistent with published descriptions of C-type inactivation, but can be explained by models in which inactivation is preferentially from closed states (which have been developed for Kv2.1 and some Ca2+ channels). We tested two predictions of preferential closed-state models: inactivation should be more rapid during a train of brief pulses than during a long pulse to the same potential, and the cumulative inactivation measured with paired pulses should be greater than the inactivation at the same time during a continuous pulse. The I channel does not behave according to these predictions, indicating that preferential closed-state inactivation does not explain the slowing of inactivation we observe at positive potentials. Inactivation of the I channel therefore differs both from C-type inactivation, as presently understood, and from the inactivation of Kv2.1., A. Babes, E. Lörinczi, V. Ristoiu, M.L. Flonta, G. Reid., and Obsahuje bibliografii
Stem cells biology is one of the most frequent topic of physiological research of today. Spinal fusion represents common bone biology challenge. It is the indicator of osteoinduction and new bone formation on ectopic model. The purpose of this study was to establish a simple model of spinal fusion based on a rat model including verification of the possible use of titanium microplates with hydroxyapatite scaffold combined with human bone marrow-derived mesenchymal stem cells (MSCs). Spinous processes of two adjacent vertebrae were fixed in 15 Wistar rats. The space between bony vertebral arches and spinous processes was either filled with augmentation material only and covered with a resorbable collagen membrane (Group 1), or filled with augmentation material loaded with 5 × 10 6 MSCs and covered with a resorbable collagen membrane (Group 2). The rats were sacrificed 8 weeks after the surgery. Histology, histomorphometry and micro-CT were performed. The new model of interspinous fusion was safe, easy, inexpensive, with zero mortality. We did not detect any substantial pathological changes or tumor formation after graft implantation. We observed a nonsignificant effect on the formation of new bone tissue between Group 1 and Group 2. In the group with MSCs (Group 2) we described mino r inflamatory response which indicates the imunomodulational and antiinflamatory role of MSCs. In conclusion, this new model proved to be easy to use in small animals like rats., K. Klíma, V. Vaněček, A. Kohout, O. Jiroušek, R. Foltán, J. Štulík, V. Machoň, G. Pavlíková, P. Jendelová, E. Syková, J. Šedý., and Obsahuje bibliografii
Stroke is despite of progressive improvements in treatment and
reperfusion strategies one of the most devastating human
pathology. However, as quality of acute health care improves and
more people survive ischemic attack, healthcare specialists have
to solve new challenges to preserve reasonable quality of life to
these patients. Thus, novel approaches which prevents
comorbidities of stroke and improve quality of life of stroke
survivors in general has to be developed and experimentally
tested. The aim of the present paper was to establish reliable rat
model of middle cerebral occlusion and set of methods allowing
selection of animals suitable for long-term experiments. We have
compared mortality rates, cerebral blood flow and extension of
ischemic lesion induced by intraluminal filament in three widely
used outbred rat strains. We have additionally used an animal
18F-DG PET scans to verify its reliability in noninvasive detection
of ischemic infarct in acute period (24 h after MCAO) for selecting
animals eligible for long survival experiments. Our data clearly
indicates that high variability between rat strains might
negatively influence stroke induction by intraluminal thread
occlusion of middle cerebral artery. Most reliable outbred rat
strain in our hands was Sprague-Dawley where maximal
reduction of cerebral blood flow and extensive ischemic lesion
was observed. Contrary, Wistar rats exhibited higher mortality
and Long-Evans rats significantly smaller or no ischemic region in
comparison to Sprague-Dawley. Additionally, we have confirmed
a positron emission tomography with 18F-fluorodeoxyglucose as
suitable method to assess extension of ischemic region in acute
period after the experimental arterial occlusion in rats.
The variations in antibody responses (total IgG and IgGl, IgG2a, IgG2b, and IgG2c subclasses) were studied in two groups of rats infected with metacercariae of the trematode Fasciola hepatica L. Animals of group 1 were 4 weeks old, and rats of group 2 were 13 weeks old. All IgG subclasses increased during the course of infection except IgG2c, which decreased. The younger rats reached more marked responses than the older, at least during the period of this trial. IgGl and IgG2a antibodies reached the highest levels, and among these two, IgG2a response was slightly superior to IgGl,
Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-κB) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-κB expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.
The activity of antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as that of the mitochondrial FAD-dependent a-glycerophosphate dehydrogenase (a-GPD) in the rat interscapular brown adipose tissue (IBAT) were studied after the treatment with methimazole (MMI) for three weeks or with iopanoic acid (IOP) for five days. Besides, the mitochondrial concentration of uncoupling protein-1 (UCP-1) and the activity of catecholamine degrading enzyme monoamine oxidase (MAO) in the IBAT as well as the activity of the catecholamine synthesizing enzyme, dopamine b-hydroxylase (DBH) in rat serum were examined. Judging by the significantly enhanced level of serum DBH, which is an index of sympathetic activity, and that of IBAT MAO, the increase in MnSOD and CAT activities in the IBAT of hypothyroid (MMI-treated) rats seems to be due to elevated activity of sympathetic nervous system (SNS). However, CuZnSOD activity is not affected by SNS. On the contrary, IOP, which is a potent inhibitor of T4 deiodination into T3 producing "local" hypothyroidism, did not change either SNS activity or activities of IBAT antioxidant enzyme. However, both treatments significantly decreased IBAT UCP-1 content and a-GPD activity suggesting that the optimal T3 concentration in the IBAT is necessary for maintaining basal levels of these key mitochondrial parameters., N. Petrović, G. Cvijić V. Davidović., and Obsahuje bibliografii
Hydrogen sulfide (H2S), an endogenous “gasotransmitter”, exists in the central nervous system. However, the central cardiovascular effects of endogenous H2S are not fully determined. The present study was designed to investigate the central cardiovascular effects and its possible mechanism in anesthetized rats. Intracerebrovent ricular (icv) injection of NaHS (0.17~17 μ g) produced a significant and dose-dependent decrease in blood pressure (BP) and heart rate (HR) (P<0.05) compared to control. The higher dose of NaHS (17 μ g, n=6) decreased BP and HR quickly of rats and 2 of them died of respiratory paralyse. Icv injection of the cystathionine beta-synthetase (CBS) activator s-adenosyl-L-methionine (SAM, 26 μ g) also produced a significant hypotension and bradycardia, which were similar to the results of icv injection of NaHS. Furthermore, the hypotension and bradycardia induced by icv NaHS were effectively attenuated by pretreatment with the KATP channel blocker glibenclamide but not with the CBS inhibitor hydroxylamine. The present study suggests that icv injection of NaHS produces hypotension and bradycardia, which is dependent on the KATP channel activation., W.-Q. Liu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of the present study was to determine the optimal initial tension, i.e. initial stretch for rat coronary artery when using the multi-wire myograph system. We used the normalization procedure to mimic physiological conditions and to stretch the coronary arterial segments to normalized internal circumference (IC 1 ). It is determined the internal circumference when the vessel relaxed under a transmural pressure of 100 mm Hg (IC 100 ), and the IC 1 is calculated by multiplying the IC 100 by a factor k. The impact of different factor k on the initial stretch and agonist- induced tension of coronary arteries were investigated. The results showed that the maximal agonist-induced tension was achieved at the factor k value of 0.90 and the initial stretch tension was given 1.16±0.04 mN/mm. The most appropriate factor k value was 0.90-0.95 and the most appropriate initial tension was 1.16-1.52 mN/mm. Th e equilibration time of the coronary artery segments should be at least 1.0 h. In the same optimal initial tension, the agonist-induced tension increased as equilibration time lengthened., N.-N. Ping ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy