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Biomedical subjects

V Kristová

Publications and source records attributed to V Kristová.

13 recordsLinked to original sources

Red wine polyphenols prevent endothelial damage induced by CCl4 administration.

It became evident in the present study that carbon tetrachloride (CCl(4)), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CC(4)/kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 microl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl(4) treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5+/-0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl(4) did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl(4) may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl(4). This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases.

Animals↗

Evaluation of endothelium-protective effects of drugs in experimental models of endothelial damage.

Endothelium-protective properties of pharmacological agents may be assessed by using different experimental models of endothelial dysfunction or injury. The model of endothelial dysfunction induced by vessel perfusion with polymorphonuclear leukocytes (PMN) was used for evaluation of pentoxifylline (PTX) effects on vasoconstrictor responses to noradrenaline (NA) in the rabbit renal artery. Addition of PMN into the perfusion solution significantly increased the responses to NA at all doses. PTX administration (10(-5) mol x l(-1)) significantly diminished the constrictor responses to NA in vessels perfused with PMN+PTX when compared to the responses in PMN-perfused vessels (at dose 0.1 microg: 32.25 vs. 14.25, at dose 1 microg: 51 vs. 27.75 (p<0.01), at dose 10 microg 74.25 vs. 39.75 (p<0.05), all values expressed as median of perfusion pressure in mm Hg). The model of endothelial damage induced by repeated NA administration in 5 doses (10-50 microg of NA) was used for evaluation of the endothelium-protective effect of sulodexide (SLX). It was found that SLX (120 U/l) significantly decreased the number of desquamated endothelial cells (EC) compared to the control group (controls: 131.4+/-20.1 EC, +SLX: 83.3+/-13.8 EC, p<0.01). These results confirmed the favorable endothelium-protective effects of pentoxifylline and sulodexide in the two experimental models.

Animals↗

Effect of indomethacin and deendothelisation on vascular responses in the renal artery.

Vasodilator prostaglandins (PGE2, PGI2) play an important role in the regulation of renal blood flow. Hence, inhibition of their production with nonsteroidal anti-inflammatory drugs increases renal vascular resistance and exerts adverse renal effects. It has been reported that besides endothelium-derived prostaglandin products, nitric oxide (NO) may be mainly involved in regulation of renal functions. The aim of our study was to evaluate the effect of cyclooxygenase inhibition with indomethacin and endothelium removal on vascular responses of the renal artery as a model vessel. Isolated segments of rabbit renal arteries were perfused at constant flow. Indomethacin administration (10(-5) mol x l(-1)) significantly increased the responses to single doses (0.1, 1, 10 microg) of noradrenaline (NA) as compared with the controls. In indomethacin-pretreated vessels, subsequent deendothelisation by air bubbles enhanced the constrictor responses to NA. In reversed order, when deendothelisation was followed by indomethacin administration, the responses to NA were similar in character. A comparison of renal artery responses to NA in both experimental situations did not reveal any significant differences. It can be supposed that endothelial and non-endothelial factors may be involved in local regulation of renal vascular tone.

Animals↗

[Endothelial diseases and endothelium-protective agents].

Endothelial dysfunction plays the key role in the development of cardiovascular system disorders. Using certain markers it is possible to evaluate the endothelial function alterations and in this way to propose the disease prognosis. Recently the number of information concerning possible reversibility of these changes and the pharmacological intervention increases. Partial data about endothelium protective properties of ACE inhibitors, hypolipidemics, pentoxifyllin, Ca2+ channel blockers, lazaroids, glycosaminoglycanes exist. In experimental conditions it is possible to evoke endothelial dysfunction and evaluate the effects of these substances. Glycosaminoglycan sulodexide reduced endothelial losses at in vitro conditions of vessel perfusion on the model of endothelium damage by vasoconstrictive stimuli. Further evidence of these substances efficacy is required for the clinical evaluation of their endothelium protective properties. The research direction in this field will certainly provide such information concerning the endothelial function moderation which may be able to change the strategy of vascular diseases pharmacotherapy. (Tab. 5, Ref. 66.)

Animals↗

Treatment of neonatal rats with monosodium glutamate attenuates the cardiovascular reactivity to phenylephrine and angiotensin II.

In rats, neonatal administration of monosodium glutamate (MSG) causes serious damage in some hypothalamic and circumventricular areas. The resulting loss of appropriate neurons important for the regulation of blood pressure (BP) may modulate cardiovascular system receptivity in these animals. In the present study, the reactivity of the cardiovascular system to intravenous injection of alpha1-adrenergic receptor agonist phenylephrine (200 microg/kg/ml) and angiotensin II (500 ng/kg in 0.6 ml for 2 min) was investigated in adult rats which had been neonatally treated with MSG or vehicle. BP parameters measured directly in conscious cannulated rats were continuously registered using a computerized system. Under basal conditions, MSG-treated rats had slightly lower systolic, diastolic and mean BP with significant differences in pulse pressure (systolic - diastolic BP). In MSG-treated animals, the maximal increase of mean arterial BP after phenylephrine and the duration of BP elevation after both agents were significantly reduced. Slopes of the linear portion of baroreceptor function curves in control and MSG-treated rats did not differ significantly, indicating that baroreflex efficacy was unchanged. The results obtained by perfusion of the hindlimb vascular bed in situ showed that the pressure responses to increasing doses of noradrenaline in MSG-treated rats were reduced. These findings demonstrate that neonatal treatment of rats with MSG lowers the responsiveness of the cardiovascular system, particularly in response to alpha-adrenergic stimulation. It is suggested that the attenuation of cardiovascular reactivity in MSG-treated rats is, at least partly, caused by diminished vascular responsiveness.

Adrenergic alpha-Agonists↗

Different reactivity of two rabbit vessels under hypoxia.

The effect of hypoxia on isolated rabbit vessel reactivity to vasoconstrictive agents was studied. Short-lasting hypoxia (30 min.) enhanced the responses to noradrenaline, 5-hydroxytryptamine, histamine and endothelin in the ear artery. Increased reactivity was also found with KCl depolarization solution. Deendothelization of the ear artery did not influence the enhanced responses to noradrenaline and endothelin in hypoxia. In similar experimental conditions the femoral artery reactivity to noradrenaline was not affected by hypoxia, the constrictory responses to 5-hydroxytryptamine were decreased. It can be concluded that hypoxic facilitation of vasoconstrictive activity is probably independent on receptor-related mechanisms and/or on the presence of endothelium. The results obtained confirm also the difference in reactivity of rabbit vessels from two vascular beds to vasoconstrictive agents under hypoxia.

Animals↗

Endothelial changes following repeated effect of vasoconstrictive substances in vitro.

Using perfusion method the reactivity of rabbit femoral and ear arteries was investigated following the administration of rising noradrenaline doses in four consecutive intervals. Progressive increase of vasoconstrictive activity of vessel segments was found. Results of histological examination showed a progressive de-endothelialization of perfused vessels. The loss of endothelium increased depending on time of action and on intensity of vasoconstrictive stimuli.

Animals↗

Evaluation of endothelium loss by in vitro vessel perfusion using millipore filters.

Endothelial loss of isolated rabbit femoral artery and renal artery was evaluated during in vitro vessel perfusion. Desquamated endothelial cells were captured on millipore filters from the perfusion solution outflow of the vessel in 3 intervals lasting 5 minutes each. In the first 5 minutes of perfusion the endothelial loss was 1,289.2 +/- 166.5 cells: in the interval after a 30 minute perfusion 4,967.9 +/- 1,428.3 cells were caught on the filters, 3.9 times more than in the first interval. During and after the 2 minutes air bubble perfusion the endothelial catch was 5.5 times greater as compared to the second interval with the average of 27,473 +/- 6,209.6 cells. The present method of quantification of the endothelial cell loss in the in vitro vessel perfusion experiment makes it possible to obtain informations about the actual state of the endothelial lining and to contribute to more precise evaluation of the modulatory effect of the endothelium on vessel reactivity to pharmacological agents.

Animals↗

[Pulmonary surfactant. Properties, relation to the respiratory distress syndrome in neonates and possibilities of its prevention and therapy].

The paper considers pulmonary surfactant with regard to the development of the lungs in the fetal period. Its biochemical properties are characterized and its value for respiratory function in neonates is assessed. Immaturity of lung tissue and of its function in preterm babies accounts for acute respiratory failure, the respiratory distress syndrome (RDS). Prevention of RDS in neonates took advantage of the knowledge obtained in experiments concerning the stimulatory effect of some mediators and hormones on the production and secretion of pulmonary surfactant. In clinical practice mostly glucocorticoids have been used, frequently in combination with beta 2 adrenergic mimetics, while aminophylline and thyroxine were used relatively rarely. The good effectiveness of ambroxol in RDS prevention has recently been demonstrated in clinical studies. The low occurrence of adverse effects potentiates the advantages of ambroxol administration. Both in RDS prevention and treatment the prospective lies with the administration of exogenous surfactant. At present effort is focusing on detecting means that would not only reduce the incidence and mortality for RDS but would also present a minimized risk for the developing organism. (Ref. 110.).

Humans↗

[Comparison of the reactivity of pulmonary tissue and pulmonary vessels in ontogenesis].

Reactivity of the lung tissue and of a. pulmonalis has been followed by means of isometric contraction of isolated strips. Histamine, acetylcholine and prostaglandin F2 alfa (PGF2 alfa) contracted the lung strips, the amplitude of histamine and acetylcholine induced contraction being significantly higher in grown guinea pigs than in foetuses. Strips of a. pulmonalis reacted with contraction in response to histamine and PGF2 alfa, they were non-reactive against acetylcholine. Magnitude of response of the strips of a. pulmonalis obtained from grown animals was significantly greater only after administration of PGF2 alfa in concentration of 10(-4) mol.l-1. Values of EC50 were significantly changed only by influence of acetylcholine on the lung strips. Isolated preparations of lung and vessel strips allow to characterize pharmacodynamic properties of the lung tissue. They represent a contribution to the evaluation of lung reactivity to xenobiotics.

Acetylcholine↗

[Changes in the vascular endothelium in fetal rabbits during perfusion in vitro].

Under perfusion conditions in vitro the morphologic state of preparations of fetal vessels of the ductus arteriosus and the pulmonary artery was studied by light and electron microscopy. At maintaining standard conditions of perfusion experiments, manipulation of vessels did not result in substantial changes of the endothelium. Storage of the vessel preparations at 4 degrees C for 24 hours did not induce marked morphologic changes, yet the vessels exhibited increased constriction reactivity to noradrenaline which resulted in severe damage of the endothelial lining. Perfusion of the ductus arteriosus by oxygen saturated solution led to vessel constriction and severe endothelial damage. The observed changes should be taken into account on evaluating responses of vascular segments to vasoactive substances.

Animals↗

Computer-based methods for measurement, recording and modeling vessel responses in vitro: a pilot study with noradrenaline.

This paper reports the first results of an ongoing methodological pilot study aimed at designing techniques for the automatic measurement and digital recording of vessel responses to biologically active substances under in vitro conditions and for the mathematical modeling of the underlying processes. The techniques presented in this pilot study allowed us to determine model-based estimates of the parameters characterizing vasoconstrictor responses, i.e., the vessel sensitivity parameter, the mean time of vasoconstrictor response and the rate constant of vessel relaxation. The given parameters are not dependent on doses of biologically active substances, provided that the underlying processes satisfy the principle of superposition. Use of these techniques is shown in the classic study of vasoconstrictor responses to noradrenaline in the rat renal artery.

Animals↗