Jerzy Bełtowski, Anna Jamroz-Wiśniewska, Ewelina Borkowska, Grazyna Wójcicka
{"title":"Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin-induced hypertension.","authors":"Jerzy Bełtowski, Anna Jamroz-Wiśniewska, Ewelina Borkowska, Grazyna Wójcicka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hyperleptinemia may be involved in the pathogenesis of obesity-associated hypertension, however, the mechanism of hypertensive effect of leptin has not been elucidated. We investigated the effect of experimental hyperleptinemia on renal function, renal Na(+), K(+)-ATPase and ouabain-sensitive H(+), K(+)-ATPase activities in the rat. Leptin administered for 7 days (0.25 mg/kg twice daily sc) decreased food intake on 6th and 7th day of treatment but had no effect on body weight. Systolic blood pressure was 30.5% higher in leptin-treated animals. Urinary excretion of sodium decreased by 35.0% following leptin treatment. Leptin had no effect on potassium and phosphate excretion as well as on creatinine clearance. The activity of Na(+), K(+)-ATPase in the renal cortex and medulla was higher in leptin-treated rats by 32.4% and 84.2%, respectively. In contrast, leptin had no effect on either cortical or medullary ouabain-sensitive H(+), K(+)-ATPase. In pair-fed group, in which food intake was reduced to the level observed in leptin-treated group, no changes in sodium metabolism and renal Na(+), K(+)-ATPase were observed. Leptin decreased urinary excretion of nitric oxide metabolites by 55.0% and urinary excretion of cGMP by 26.3%. Plasma concentration of atrial natriuretic peptide tended to be higher and urinary excretion of urodilatin was 64.9% higher in leptin-treated animals. These data suggest that hyperleptinemia decreases natriuresis by up-regulating Na(+), K(+)-ATPase and stimulating tubular sodium reabsorption. This effect is mediated, at least in part, by deficiency of nitric oxide (NO). Abnormal renal sodium retention and vasoconstriction associated with NO deficiency may contribute to leptin-induced hypertension and to blood pressure elevation in hypertensive obese individuals.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 2","pages":"213-22"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24529941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrzej Królicki, Adam Klimowicz, Stanisława Bielecka-Grzela, Adam Nowak, Romuald Maleszka
{"title":"Penetration of cotrimoxazole components into skin after a single oral dose. Theoretical versus experimental approach.","authors":"Andrzej Królicki, Adam Klimowicz, Stanisława Bielecka-Grzela, Adam Nowak, Romuald Maleszka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Concentrations of trimethoprim and sulfamethoxazole in plasma, cantharidin-induced skin blister fluid and theoretical peripheral compartment were determined in twelve male subjects suffering from bacterial skin diseases after a single oral dose of 0.32 g of trimethoprim and 1.6 g of sulfamethoxazole. Maximum trimethoprim concentrations of 8.5 +/- 1.1 micromol/l in plasma, 5.6 +/- 0.8 micromol/l in blister fluid and 5.8 +/- 2.2 micromol/l in theoretical peripheral compartment were found after 3 +/- 1, 7 +/- 2 and 9 +/- 6 h, respectively. Degree of penetration into blister fluid and theoretical peripheral compartment was 0.94 +/- 0.23 and 1.05 +/- 0.09, respectively. The differences between respective pharmacokinetic parameters of trimethoprim in blister fluid and theoretical peripheral compartment were statistically insignificant. Maximum sulfamethoxazole concentrations of 295 +/- 47 micromol/l in plasma, 182 +/- 46 micromol/l in blister fluid and 239 +/- 58 micromol/l in theoretical peripheral compartment were found after 3 +/- 1, 8 +/- 2 and 7 +/- 4 h, respectively. Degree of penetration into blister fluid and theoretical peripheral compartment was 0.82 +/- 0.20 and 1.04 +/- 0.02, respectively. In contrast to trimethoprim, the differences between respective pharmacokinetic parameters of sulfamethoxazole in blister fluid and theoretical peripheral compartment, except time to maximum concentration, were statistically significant. Cantharidin-induced skin blister fluid method can be used to estimate drug penetration into skin. Due to differences between the respective pharmacokinetic parameters in experimental and theoretical peripheral compartment, in some cases evaluation of drug penetration into skin should not be replaced by the theoretical peripheral compartment calculation.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 2","pages":"257-63"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24529947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is anorexia in thioacetamide-induced cirrhosis related to an altered brain serotonin concentration?","authors":"Saida Haider, Sadia Saleem, Saima Shameem, Shahida P Ahmed, Tahira Parveen, Darakhshan J Haleem","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Anorexia or loss of appetite, one of the most typical symptoms observed in experimental and human cirrhosis, has been proposed to be associated with altered brain serotonin (5-HT) metabolism. In order to evaluate this hypothesis, brain 5-HT, its precursor tryptophan (TRP) and its metabolite 5-hydroxyindole-acetic acid (5-HIAA) were measured in brains of rats with thioacetamide (TAA)-induced liver cirrhosis. Thioacetamide at a dose of 500 mg/l in drinking water was administered for 6 weeks and during this period food intake was carefully measured in order to monitor the loss of appetite or decrease in food intake observed in cirrhosis. Concentrations of brain TRP, 5-HT and 5-HIAA were measured by HPLC with electrochemical detection. In TAA-treated rats, concentrations of 5-HT, TRP and 5-HIAA were increased in brain (44%, 33% and 36% of controls, p < 0.01). In plasma and liver of cirrhotic rats, TRP levels were increased (195% and 43%; p < 0.01). Plasma glucose and albumin levels were decreased (50%; p < 0.01 and 31%). Food intake, growth rate and locomotor activity of TAA-treated rats also decreased (73%, 22% and 73% of controls; p < 0.01). The results of this study show that brain 5-HT concentration in rats is increased in TAA-treated rats and it may, therefore, play an important role in the pathogenesis of anorexia associated with TAA-induced cirrhosis.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"73-8"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gamma-hydrobutyric acid (GHB) and its chemical modifications: a review of the GHBergic system.","authors":"Anna Waszkielewicz, Jacek Bojarski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Gamma-hydroxybutyric acid (GHB) is a naturally occurring substance with function of an inhibitory neurotransmitter in the central nervous system in mammals. GHB can be used as a medicine in narcolepsy (Xyrem) and for general anesthesia (sodium oxybate). It is also a popular drug of abuse, causing coma, addiction and severe withdrawal syndrome, and, therefore, demanding thorough studies on the GHBergic system and expanded research on toxicology of this compound. The aim of this review is to present the proved and some suggested mechanisms of its action from pharmacological point of view, which may help to properly treat intoxication or other pathological states caused by GHB ingestion. Some new GHB derivatives studied for analogous action and their present use are also described.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"43-9"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nandita Das, Tapasi Das Chowdhury, Aindrila Chattopadhyay, Asoke G Datta
{"title":"Attenuation of oxidative stress-induced changes in thalassemic erythrocytes by vitamin E.","authors":"Nandita Das, Tapasi Das Chowdhury, Aindrila Chattopadhyay, Asoke G Datta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The oxidative stress status of the transfusion-dependent Ebeta- and beta-thalassemia patients were studied before and after treatment with vitamin E for a period of four weeks. The level of cellular vitamin antioxidants viz. ascorbic acid and vitamin E in the thalassemia patients were found to be considerably lower compared to normal subjects. The activities of enzymatic antioxidants viz. catalase, glutathione peroxidase and glutathione reductase were found to be drastically reduced in untreated Ebeta- and beta-thalassemic patients when compared to normal subjects. However, the activity of superoxide dis-mutase was found to be increased in both types of untreated thalassemic patients when compared to normal individuals. An increase in superoxide dismutase and a decrease in catalase activity reflects the presence of a severe oxidative stress situation in the erythrocytes of the untreated transfusion dependent Ebeta- and beta-thalassemia patients. Changes in erythrocyte membrane protein pattern in untreated Ebeta- and beta-thalassemia patients when compared to normal erythrocyte further confirm the presence of continued oxidative stress in the ailing thalassemic erythrocytes. All these changes in the antioxidant status as well as the changes in the erythrocyte membrane proteins are ameliorated to considerable extent when the transfusion-dependent Ebeta- and beta-thalassemia patients were treated with vitamin E at a dose of 10 mg/kg/day for a period of four weeks. The patients during the treatment period did not exhibit any side effects and gained in body weight indicating a healthy status. The present study reveals that the lipophilic antioxidant vitamin E could be useful in the management of transfusion-dependant Ebeta- and beta-thalassemia patients.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"85-96"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Włodzimierz Buczko, Andrzej Kubik, Iwona Kucharewicz, Ewa Chabielska
{"title":"Antithrombotic effect of captopril and enalapril in young rats.","authors":"Włodzimierz Buczko, Andrzej Kubik, Iwona Kucharewicz, Ewa Chabielska","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Angiotensin converting enzyme inhibitors (ACE-Is) are the main drugs used in the treatment of essential hypertension and congestive heart failure in adults. Recently, we have demonstrated the antithrombotic effect of captopril (CAP) and enalapril (ENA) in venous thrombosis model in adult rats. One might also suggest the beneficial effect of those drugs on hemostasis in young individuals. Two months old male Wistar rats were used in the study. Acute administration of CAP at a dose of 50 and 100 mg kg(-1) significantly reduced the venous thrombus weight. Dose-dependent reduction in the thrombus weight was also observed in ENA (3, 10, 30 mg kg(-1))-treated rats. Strong reduction in the thrombus weight was also seen after chronic administration of CAP (2 x 25 mg kg(-1)) and ENA (1 x 15 mg kg(-1)). Both drugs given chronically reduced the frequency of thrombi. Systolic blood pressure was reduced to similar extent after acute and chronic application of the drugs. CAP shortened euglobulin clot lysis time (ECLT) when given acutely (100 mg kg(-1)) and chronically (2 x 25 mg kg(-1)). ENA decreased ECLT only when given at multiple doses (1 x 15 mg kg(-1)). None of the drugs changed prothrombin time or activated partial tromboplastin time. We conclude that CAP and ENA possess antithrombotic effect in young individuals. Activation of the fibrinolytic pathway seems to play an important role in the mechanism of their antithrombotic action.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"97-104"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adrenomedullin--what do we know 10 years since its discovery?","authors":"Jerzy Bełtowski, Anna Jamroz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Adrenomedullin (ADM) is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide (CGRP) initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla, endothelial and vascular smooth muscle cells, myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor (CRLR), a member of serpentine receptor superfamily, and receptor activity modifying protein (RAMP) type 2 or 3. ADM has also some affinity for CGR(1) receptor composed of CRLR and RAMP1. ADM dilates blood vessels in both endothelium-dependent and independent manner and decreases systemic arterial pressure. Intrarenally administered ADM increases natriuresis by vascular and tubular mechanisms. In addition, ADM inhibits migration and proliferation of vascular smooth muscle cells and attenuates myocardial remodelling by inhibiting protein synthesis in cardiomyocytes and proliferation of cardiac fibroblasts. ADM is expressed in various tissues from early stage of embryogenesis and is also synthesized in placenta, uterus and fetal membranes. Plasma ADM level is increased in arterial hypertension, acute coronary syndromes, heart failure, renal diseases and septic shock, being involved in the pathophysiology of these disorders. Experimental ADM treatment is beneficial in arterial and pulmonary hypertension, heart failure, septic shock and ischemia/reperfusion injury. Proadrenomedullin N-terminal peptide (PAMP) is another product of ADM gene which is co-secreted by ADM-producing tissues, with some effects similar and some opposite to ADM.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"5-27"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jolanta Parada-Turska, Mirosław Czuczwar, Jacek Kiś, Piotr Czuczwar, Anna Cioczek, Jarogniew Łuszczki, Stanisław J Czuczwar
{"title":"Allopurinol does not affect the anticonvulsant activity of carbamazepine and valproate in maximal electroshock-induced convulsions in mice.","authors":"Jolanta Parada-Turska, Mirosław Czuczwar, Jacek Kiś, Piotr Czuczwar, Anna Cioczek, Jarogniew Łuszczki, Stanisław J Czuczwar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Allopurinol, an inhibitor of xanthine oxidase, is indicated in the management of patients with elevated serum and urinary uric acid levels. It was also reported to be beneficial in patients with epilepsy when added to traditional antiepileptic drug. Here, we investigated the effect of allopurinol upon the electrical seizure threshold and its effect on the protective efficacy of common antiepileptic drugs, carbamazepine (CBZ) and valproate (VPA) against maximal electroshock (MES)-induced convulsions in mice. We found that allopurinol administered at doses of 5, 15 or 45 mg/kg, did not affect electrical seizure threshold. When administered acutely or for a prolonged period of time (5 times every 24 h), it did not affect anticonvulsant activity of CBZ and VPAin MES. Free plasma concentration of both anticonvulsants was not affected by allopurinol given at a dose of 45 mg/kg for 5 days. Thus, our results did not support suggestions that allopurinol can be beneficial as add-on drug in the management of epilepsy at least in patients treated with CBZ or VPA.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"67-72"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucyna Jóźwiak, Krzysztof Łukawski, Stanisław J Czuczwar, Maria Sieklucka-Dziuba
{"title":"Competitive NMDA receptor antagonists and agonists: effects on spontaneous alternation in mice exposed to cerebral oligemia.","authors":"Lucyna Jóźwiak, Krzysztof Łukawski, Stanisław J Czuczwar, Maria Sieklucka-Dziuba","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The purpose of the present study was to investigate the effects of competitive NMDA receptor antagonists,D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) and its ethyl ester (CGP 39551), or agonist, N-methyl-D-aspartate (NMDA) on spontaneous alternation in mice exposed to cerebral oligemia. Alternation behavior was evaluated in an Y-maze. Transient cerebral oligemic hypoxia was induced by bilateral clamping of carotid arteries (BCCA) for 30 min under pentobarbital anesthesia. In BCCA mice, CGP 37849 (5 mg/kg, ip) impaired spontaneous alternation when given 48 h or 7 days after surgery. CGP 39551 (5 mg/kg, ip) had no effect.NMDA (50 mg/kg, sc) improved performance of the task in BCCA mice when tested 48 h after surgery. These results suggest that cerebral oligemic hypoxia induced by BCCA leads to functional disturbances in the central nervous system, such as spontaneous alternation impairment and increased susceptibility to NMDA receptor-related drugs. Adverse potential of cerebral oligemia may limit a therapeutic use of NMDA receptor antagonists.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"59-66"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viola Tamási, Zsuzsanna Riedl, Ottó Dobozy, András Falus, László Vereczkey, Katalin Monostory
{"title":"In vitro induction of cytochrome P450 enzymes in hepatocytes isolated from the regenerating rat liver.","authors":"Viola Tamási, Zsuzsanna Riedl, Ottó Dobozy, András Falus, László Vereczkey, Katalin Monostory","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Partial hepatectomy results in the loss of cytochrome P450 enzymes. During regeneration, the levels of cytochrome P450 activities, apoproteins and mRNA are reduced. Our present study investigated CYP1A, CYP2E1 and CYP3A induction in the cells of rat liver regenerating for 1, 3, 7, or 14 days. Hepatocytes were isolated from regenerating liver of hepatectomized rats and treated with enzyme inducers: 3-methylcholanthrene, imidazole and dexamethasone. CYP1A enzymes of the cells isolated from regenerating liver were inducible by 3-methylcholanthrene. The rate of induction of the cells from 3-day regenerating liver by 3-methylcholanthrene was three times higher than that of the hepatocytes of sham-operated rats. Dexamethasone caused about two- or three-fold stronger elevation of CYP3A in the cells of 1-, 3- and 7-day regenerating liver than in hepatocytes of sham-operated animals. However, the degree of CYP2E1 induction by imidazole was the same (about 2.5-fold) at each regenerating time as it was detected in the hepatocytes of sham-operated animals. In conclusion, the inducibility of the cells was retained at each regenerating time, but the degree of induction showed some differences.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 1","pages":"113-9"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}