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Biomedical subjects

M Wutkiewicz

Publications and source records attributed to M Wutkiewicz.

At least 19 recordsLinked to original sources
PubMed1994

Antihypertensive treatment with beta blockers and gabaergic transmission in rat brain.

The effects of chronic oral administration of propanolol and metoprolol on blood pressure and GABAergic function were investigated in spontaneously hypertensive rats (SHR) and compared with the effect of dihydralazine. Under the experiment conditions employed all drugs reduced significantly (p < 0.01) arterial pressure. The beta blockers elevated GABA turnover in the hypothalamus and the pons-medulla. Dihydralazine, however had not such an effect. Our result suggest that the antihypertensive action of beta blockers may be related in part to the enhanced cerebral GABAergic transmission.

Adrenergic beta-Antagonists↗
PubMed1993

Enhancement of GABAergic system activity by metoprolol in spontaneously hypertensive rats.

The relevance of the GABAergic system for the antihypertensive action of metoprolol in spontaneously hypertensive rats was studied by comparing the effect of metoprolol with the effect of dihydralazine. Chronic oral treatment with metoprolol produced the maximum effect after 49 days (-delta 34 mm Hg). This effect persisted on the same level for up to 55 days. The measurements of gamma-aminobutyric acid (GABA) synthesis and specific [3H]GABA binding were performed in the hypothalamus, the pons-medulla, the hippocampus and the striatum. Significant stimulation of GABA synthesis and turnover appeared in the hypothalamus and the pons medulla. In contrast, chronic administration of dihydralazine had no influence on GABA synthesis rate. It was also shown that metoprolol elevated significantly (P < 0.01) specific [3H]GABA binding in the hypothalamus and the pons-medulla. In the striatum this effect of metoprolol was less pronounced. Binding constant analysis revealed changes in both the receptor density and affinity. Our results suggest that the hypotensive response to chronic treatment with metoprolol might be attributed to an enhancement of GABAergic system activity.

Analysis of Variance↗
PubMed1993

Acute systemic toxicity and antihypertensive activity of a novel todralazine analog in rats.

Acute intravenous toxicity and antihypertensive activity of KB1, a novel todralazine analog was investigated and compared with the effects of todralazine (Td) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. LD50 values were 72 mg.kg-1 for KB1, and 255 mg.kg-1 for Td in WKY and 43 mg.kg-1 or KB1 in SHR. Therefore, the toxicity of KB1 was higher than that of Td and it increased in SHR. The antihypertensive activity of KB1 (ED20% 9.8 mg.kg-1) in WKY was about 9 times less potent in comparison with Td (ED20% 1.1 mg.kg-1). Blood pressure reducing activity of KB1 augmented apparently in SHR (ED20% 2.5 mg.kg-1) whereas Td had not such an effect (ED20% 1.0). Thus, the influence of Td on blood pressure was similar in normotensive and hypertensive animals. Our results indicate that KB1 is capable of reducing blood pressure preferentially in hypertension.

Animals↗
PubMed1993

Systemic toxicity and dermal irritation of Tołpa Peat Preparation.

The systemic toxicity of the peat preparation in rats and rabbits was assessed. Dermal irritation tests were conducted on rabbits. In acute and chronic toxicity studies TPP was well tolerated in both animal species. Laboratory findings revealed no hematologic abnormalities as well as disturbances in liver and kidney function. No local irritancy of TPP was found. The results show that TPP may be considered as practically non toxic.

Amino Acids↗
PubMed1992

Increased activity of the GABAergic system in selected brain areas after chronic propranolol treatment in spontaneously hypertensive rats.

The influence of chronically administered propranolol on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system in spontaneously hypertensive rats was studied and compared with the effect of dihydralazine. GABA content, synthesis and turnover rate in selected brain areas were assessed. Hypotensive activity of propranolol and dihydralazine after injection of GABA antagonist pictrotoxin was examined in acute experiment. Prolonged administration of propranolol increased GABA content, synthesis and turnover rate in the hypothalamus and the pons-medulla. After chronic injections of dihydralazine there was no change in GABA indices. Antihypertensive activity of dihydralazine in picrotoxin-treated animals remained unchanged. On the contrary, picrotoxin suppressed the propranolol-induced decrease in blood pressure. Our results indicate that propranolol increases GABAergic system activity. Therefore, we conclude that down-regulation of the GABAergic system in hypertension may be compensated by the regulatory action of propranolol.

Aminooxyacetic Acid↗
PubMed1992

Pharmacological effects of Ukrain in rats and rabbits.

The effect of Ukrain administered in various doses on mean blood pressure (MAP) and breathing rate in rats and rabbits was evaluated. It was found that MAP was reduced and breathing rate increased significantly in both animal species. Maximum tolerated dose (MTD) of Ukrain was 10-fold higher in rats than in rabbits, and it amounted to 3.5 mg x kg(-1) and 0.35 mg x kg(-1), respectively. Possible clinical implications of these findings were discussed.

Alkaloids↗
PubMed1991

Effect of clonidine on blood pressure and GABAergic mechanisms in spontaneously hypertensive rats.

The action of clonidine on blood pressure and on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system was studied. A single injection of clonidine (1, 5, 10, 20 micrograms.kg-1) induced a dose-dependent decrease of blood pressure. Chronic administration of clonidine, 10 micrograms.kg-1, produced the maximum effect after the third injection. The effect was maintained for the duration of the study. Single or chronic clonidine injections, at the dose of 10 micrograms.kg-1 enhanced the GABA content in the brain and hypothalamus. This effect was less pronounced in the hippocampus. The drug administered according to the same regimen stimulated glutamic acid decarboxylase activity only in the hypothalamus. Clonidine caused a marked enhancement of specific [3H]GABA binding in the hypothalamus. These data suggest that the hypotensive action of clonidine is related to stimulation of the GABAergic system.

Animals↗
PubMed1991

Propranolol effect on GABA synthesis rate estimated by two different methods.

The propranolol effect on GABA synthesis rate in some brain structures using two different method was assessed. Both methods gave comparable results. Evaluation of the synthesis rate in vivo after inhibition of GABA degradation supplied more adequate information indicating that the availability of GABA precursor in the hypothalamus and the hippocampus is limited.

Animals↗
PubMed1984

Influence of some sulfhydryl compounds on the antineoplastic effectiveness of 5-fluorouracil and 6-mercaptopurine.

The influence of three chosen model sulfhydryl groups containing compounds, characterized by increasing size of molecule--cysteine, glutathione and insulin on antineoplastic activity of 5-fluorouracil (5-FU) and 6-mercaptopurine (6-MP) against murine leukemia L-1210 5-FU and 6-MP and murine sarcoma Sa 180, was studied. Sulfhydryl compounds failed to change in most cases the therapeutic (antineoplastic) effect of 5-FU and 6-MP. However, certain doses of these sulfhydryl compounds enhanced the cytostatic effect of 6-MP in respect to Sa-180.

Animals↗
PubMed1979

Influence of insulin on pharmacokinetics of mannosulfan in rats.

The purpose of the present study was to investigate the possibilities of potentiation of the antitumor action of mannosulfan after its administration together with insulin. The pharmacokinetics of mannnosulfan were investigated after its administration separately and together with insulin. Concentrations of mannosulfan in the plasma were determined by gas chromatography. Insulin enhanced the rate of absorption of mannosulfan from the peritoneal cavity and prolonged its elimination from the body. It may be assumed that insulin enhances not only passage of mannosulfan from the peritoneal cavity to blood, but also from blood to tissues. Since increased antitumor effectiveness of mannosulfan was accompanied by its decreased toxicity, it may be concluded that insulin causes selective cummulation of the cytostatic only in some tissues, among others, in the tumor.

Animals↗
PubMed1977

[Development of a standard model of nutritional liver injuries which could be used in experimental pharmacology].

This work was undertaken to elaborate a standard model of nutritional liver injury similar to that occurring in the deficiency states in human pathology with regard to functional troubles and morphological lesions. Rats of the Wistar strain were fed two low protein diets (diet A and diet B) containing however the full composition of vitamins and minerals. The diet A showed the most advantages as it provoked mild liver changes; but it proved to induce continuous impairment of the liver function in parallel direction with the parenchymal lesions. The full correlation of the morphological lesions and the functional disturbances observed in experimental animals as well as their intimate ressemblance to the clinical picture and hepatic lesions encountered in the deficiency states in human pathology suggest that present model of nutritional liver injury could be useful in experimental pharmacology.

Age Factors↗
PubMedDate not supplied

Down-regulation of the GABA-ergic system in selected brain areas of spontaneously hypertensive rats (SHR).

The relevance of GABA-ergic system in hypertensive state has been studied. GABA content, GAD activity and GABA-A receptor binding in various brain areas in age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY) was compared. Out of 9 brain areas studied the GABA content was significantly lower in the substantia nigra, hypothalamus, hypothalamus posterior and hippocampus of SHR rats. GAD activity was lowered in the hypothalamus and hippocampus of young SHR and adult SHR rats (4, 8, 14 weeks old). Scatchard analysis of the binding isotherms indicated a lower Bmax of the binding sites in the hypothalamus and hippocampus of 8 and 14 weeks old SHR rats. These results suggest that activity of GABA-ergic system differs substantially in SHR and WKY rats brain. Furthermore, these differences appear already in young prehypertensive SHR rats as well as in the early stages of hypertension.

Aging↗