Acta physiologica et pharmacologica Bulgarica最新文献

{"title":"Chronopharmacology and its impact on antihypertensive treatment.","authors":"B Lemmer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Circadian rhythms have been documented throughout the plant and animal kingdom at every level of eukariotic organization. Circadian rhythms are endogenous in nature, driven by oscillators or clocks, and persist under free-running (e.g. constant darkness) conditions. The genes expressing the biological clock have been identified in various species. The important feature of endogeneous biological rhythms is their anticipatory character. Rhythmicity inherent to all living systems, allows them to adapt more easily and to better survive under changing environmental conditions during the 24 hours of a day as well as during changing seasons. Having this in mind it is easy to conceive that not only must the right amount of the right substance be at the right place, but also this must occur at the right time. Also in man nearly all functions of the body including those influencing pharmacokinetic parameters such as drug absorption and distribution, drug metabolism and renal elimination display significant daily variations. Also the onset and symptoms of diseases such as coronary infarction, angina pectoris, stroke, ventricular tachycardia are circadian phase dependent. Myocardial infarction and angina attacks as well as silent ischemias (ST-segment depression) in stable angina pectoris have an early morning peak between 8-12 h. In contrast, ECG abnormalities and angina attacks in variant angina mainly occur at night. Blood pressure and heart rate in normotensives and essential (primary) hypertensive patients display highest values during daytime followed by a nightly drop and an early morning rise. In about 70% of forms of secondary hypertension (e.g. renal disease, hyperthyroidisms, hormonal diseases, gestational hypertension), however, this rhythmic pattern is abolished or even reversed exhibiting nightly peaks in blood pressure. This form of hypertension is accompanied by increased end organ damages. Thus, different subtypes of a disease (angina pectoris, hypertension) can display different circadian patterns in symptoms. These observations are a challenge for basic and clinical research to get a better understanding on the underlying mechanisms of regulation. Moreover, they call for a circadian time-specified drug treatment. From above it is evident that pharmacokinetics may also not be constant within a day. Chronopharmacokinetics have been shown for several cardiovascular active drugs (propranolol, nifedipine, verapamil, enalapril, isosorbide-5-mononitrate, digoxin, etc.). Far more drugs were shown to display significant daily variations in their effects (chronopharmacodynamics, chronotoxicology) even after chronic application or constant infusion. In conclusion, there is clear evidence that the dose/concentration-response relationship of drugs can be significantly dependent on the time of day. Thus, circadian time has to be taken into account as an important variable influencing a drug's pharmacokinetics and/or its effects or side effects.</p","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21587424","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":"Renal excretory function in conscious Long Evans and vasopressin deficient (Brattleboro) rats after endothelin-A receptor inhibition.","authors":"R Girchev,&nbsp;P Markova,&nbsp;D Mikhov,&nbsp;N Natcheff","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>All experiments were performed on conscious, freely moving male Long Evans as well as Diabetes incipidus (Brattleboro) rats (300-320 g). The endothelin-A (ETA) receptor antagonist BQ-123 (Neosystem) was administered through femoral vein cannula. Arterial blood pressure was measured trough femoral artery catheter. The bladder was cannulated for urine collection via a small suprapubic incision. After a 40 min control period BQ-123 infusion (16.4 nmol/kg/min, 25 microliters/min) was started and continued for 50 min. The effect of 32.8 nmol/kg/min BQ-123 infused in conscious Brattleboro rats was also investigated. Plasma and urine concentrations of sodium, potassium and chloride as well as osmolality were determined. Glomerular filtration rate (GFR) was estimated using the clearance of endogenous creatinine. Endothelin-A receptor inhibition by 16.4 nmol/kg/min BQ-123 infusion in conscious Long-Evans rats decreased urine flow rate by 38.4% (p < 0.02) and increased urine osmolality by 30.3% (p < 0.05). Sodium, potassium, chloride excretion did not alter. Endothelin-A receptor inhibition by 16.4 nmol/kg/min and by 32.8 nmol/kg/min BQ-123 infusion in conscious Brattleboro rats did not produce any change in urine flow rate, urine osmolality or excretion of the electrolytes studied. Endothelins acting via ETA receptors may function as an inhibitor of water reabsorption in the kidneys of conscious rats.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21525494","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":"Spectral analysis of heart rate and arterial pressure variability after nitric oxide synthase inhibition.","authors":"D Mikhov,&nbsp;P Markova,&nbsp;R Girchev","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The experiments were performed on male, conscious Wistar rats. Femoral arterial pressure was registered by Statham GOULD P23 ID pressure transducer connected to MP 100WS BIOPAC work station after analog to digital conversion during 40 minutes long control period. Nitric oxide synthase inhibition was performed by injection of 100 microliters, 10 mg/kg b.w. N-omega-nitro-L-arginine methyl ester (L-NAME) in saline through femoral vein catheter. Twenty minutes later arterial pressure registration was started and was continued for 40 minutes. The pulse-by-pulse values of systolic, diastolic and mean arterial pressure as well as the pulse intervals were measured by peak and rate detectors of the AcqKnowledge 2.0 software. Row data were processed using a virtual instrument developed in our laboratory in the graphical programming environment Lab VIEW 3.1.1. L-NAME increased systolic, diastolic and mean arterial pressure by 16.6%, 25% and 35%, respectively. The PMF/PHF ratio in heart rate spectrum decreased, indicating an increased vagal effect on the heart. Nitric oxide synthase inhibition increased the low-frequency component of systolic arterial blood pressure variability by 39.5%. Nitric oxide is a physiological regulator of rapid fluctuations of arterial blood pressure.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21525495","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":"Non-invasive registration of the aboral and oral spreading of the gastroduodenal peristaltic activity (experimental and clinical investigations).","authors":"E Atanassova,&nbsp;B Damianov,&nbsp;P Gurkov,&nbsp;V Kolev","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The electrical activity of the stomach and the upper part of the small intestine of healthy volunteers and patients with nausea and vomiting was recorded non-invasively on an original electrogastrograph. Two kinds of waves were distinguished according to their amplitude: low-amplitude waves, corresponding to the period of quiescence of migrating myoelectrical complex (MMC) and about twice higher in amplitude waves, characterising the periods of activity of MMC (peristaltic activity). There was also some difference between the low- and high-amplitude waves from the small intestine. Sequence of high-amplitude waves recorded from the stomach was followed usually by sequence of high-amplitude waves from the small intestine, presenting the aboral spreading of an activity period of MMC from the stomach to the small intestine. In some patients however, high-amplitude waves were led off first from the duodenal record and after that high-amplitude waves appeared in the gastric record. This suggests an oral spreading of the peristaltic activity (antiperistalsis). Experimental model of antiperistalsis was performed on dogs with chronically implanted electrodes on the gastric and duodenal muscle wall. Carbachol 5 micrograms/kg i.m. evoked bursts of spike potentials first with duodenal slow waves and after that with the gastric slow potentials. The antiperistaltic spreading of the spike activity in dog corresponded to the appearance of high-amplitude waves first in the record of the human small intestine, followed by sequence of high-amplitude waves in the stomach. Thus, the non-invasive recording of the electrical activity of the stomach and small intestines gives reliable information about the direction of the spreading of the peristaltic activity.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21215901","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":"Frog muscle fibre action potential and different extracellular calcium concentration at lowered pH in the medium.","authors":"N Radicheva,&nbsp;K Mileva,&nbsp;V Martinov","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This article is mainly concerned with the influence of Ca2+[o in acidified extracellular medium on the intracellular action potentials (ICAPs) and total ionic current (Ii) during ICAP of isolated skeletal muscle fibre. The bundles of frog muscle fibres were bathed in Ringer's solution with standard Ca2+[o at pH 6.5 after which the fibres were exposed for 30 min to Ca(2+)-free solution and Ca(2+)-enriched solution at pH 6.5. The ICAPs in standard Ca2+[o solution (control) and after exposure for 30 min to Ringer's solutions with different Ca2+[o at pH 6.5 were recorded and the Ii during ICAP was calculated. The ICAP amplitude from the fibres in Ca(2+)-free solutions at pH 6.5 showed a significant increase vs. control, while the time characteristics if the ICAPs in different Ca2+[o decreased except for the ICAP depolarization phase duration in Ca(2+)-enriched solution. The Ii alterations reflect ICAP changes. It was suggested that the changed Ca2+[o at pH 6.5 compensated to some extent the observed inhibitory effect of lowered pH on ICAP parameters in solution with standard Ca2+[o.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21525499","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":"alpha-Tocopherol and reduced glutathione deficiency and decreased deformability of erythrocytes after thermal skin injury.","authors":"G Bekyarova,&nbsp;T Yankova","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Burns are followed by oxidative changes in red blood cells, probably as a result of ischemia/reperfusion which takes place in the microvasculature of the injured tissues. This leads to a marked decrease in the erythrocyte deformability, one of the most prominent factors for haemorheological disorders in the early post-burn period. We found that at the 24 th hour after burn skin injury of rats, the decrease in erythrocyte deformability was accompanied by an increase of fluorescent product levels in red blood cells. The erythrocyte systems for antioxidative protection fail to control the oxidative burst after burning. This was due to the decreased concentration of vitamin E (a-tocopherol) and reduced glutathione (GSH) and the increased oxidized glutathione (GSSG) in red blood cells. Both alpha-tocopherol and GSH-deficiency potentiate the susceptibility of red blood cells to oxidative membrane injury, and decrease the deformability of thermally affected erythrocytes. Treatment with alpha-tocopherol (20 ml/kg b.m., immediately after thermal skin injury) prevented the vitamin E reduction and peroxidative membrane damage of erythrocytes and improved their deformability. These results provided strong evidence that the decreased erythrocyte deformability is partly related with alpha-tocopherol deficiency and oxidative membrane damage of red blood cells in the early post burn period.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21216502","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":"Influence of aluminium on erythropoiesis, iron metabolism and some functional characteristics of erythrocytes in rats.","authors":"T Ganchev,&nbsp;E Dyankov,&nbsp;R Zacharieva,&nbsp;I Pachalieva,&nbsp;M Velikova,&nbsp;B Kavaldjieva","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The increased aluminium (Al) levels in serum of patients with chronic renal failure on hemodialysis are associated with impaired erythropoiesis and iron metabolism. The long term Al loading of rats (20 to 90 days) has similar effect. Data are still lacking about the effects after short-term aluminium treatment. The 7 day's treatment with Al2(SO4)3 in a dose 67.5 mg/kg b. w., i. m. m. significantly decreased hemoglobin, hematocrit, incorporation of 59Fe in newly formed erythrocytes and increased reticulocytes in absolute and relative counts. We observed a mild degree hypochromic, ferropenic, microcytic anemia and polychromazia in the available macrocytes. The immature erythroblasts were predominant forms in the erythroblastogram while the number of mature erythroblasts was decreased. Index of maturation of erythroblasts was lower, indicating inhibited erythroblast maturation. Plasma iron, TIBC, transferrin saturation and 59Fe absorption in the experimental group were significantly decreased. Spontaneous and mechanical hemolysis of erythrocytes were lower while erythrocyte deformability was increased. Obviously, Al treatment inhibits erythropoiesis and iron metabolism, probably hinders hemoglobin synthesis and erythroid cell maturation but does not affect the studied functional characteristics of mature erythrocytes negatively.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21215903","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":"Behavioral changes as a result of dotarizine or flunarizine influence on dopaminergic neurotransmission in the striatum.","authors":"V D Petkov,&nbsp;B Petkova","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In experiments on rats, we studied the changes in stereotypy induced by apomorphine (2.5 mg/kg i.p.) or amphetamine (2 mg/kg i.p.) and in haloperidol (1 mg/kg i.p.) catalepsy in rats treated with dotarizine (25 mg/kg orally), flunarizine (25 mg/kg) or vehicle for 10 days. Dotarizine did not induce any significant changes in the intensity and duration of apomorphine- or amphetamine-induced stereotypy nor in haloperidol-induced catalepsy. The flunarizine-induced changes in the behavioral effects of apomorphine, amphetamine and haloperidol suggest the decrease of striatal dopaminergic neurotransmission, whereby the risk of occurrence of extrapyramidal side effects of the drug when used in clinical practice. Dotarizine is not associated with such a risk.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21215902","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":"Perceptual grouping of strip dot patterns.","authors":"N Bocheva,&nbsp;N Yakimoff,&nbsp;P Vos","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Grouping of one-dimensional (strip) dot patterns was investigated, using an adjustment procedure to evaluate the distance (adjusted gap) at which two patterns appear to merge in a single strip. The size of the patterns had only a scaling effect on the adjusted gap. The adjusted gap and the variance of the estimates were influenced by the number of dots and the regularity (similarity, symmetry) of the patterns in the pair. Models of proximal grouping failed to account for the results obtained. A two-stage process implying determination of dot location and evaluation of inter-dot separation by means of \"eclectic units\" (Morgan, Hole & Glennerster, 1990) was considered to explain the findings.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21215972","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":"Altered response characteristics of cat visual neurons after systemic administration of the dihydropyridine calcium antagonist nimodipine.","authors":"H J Koch","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nimodipine, a cerebrovasotropic dihydropyridine calcium antagonist, has gained increasing interest in geriatric research during last years and is discussed with regard to its possible involvement in restoration and preservation of brain plasticity. Single unit responses were recorded by microelectrodes in the visual cortex of anaesthetized adult cats. Receptive fields were stimulated with light bars moved forward and backward or flashed On/Off. Neuronal activity was recorded before and 5 and 30 min after i.v. administration of 0.1 mg/kg nimodipine. On the basis of penstimulus-time-histograms (PSTH) the response was analysed. There was a marked variability of the response after stimulation with both stationary and moving bars. Median firing rate was reduced 5 min after injection following On-stimulation but generally rose 30 min both after stimulation with light bars flashed On or Off Following stimulation with moving light bars about 60% of neurons showed decreased firing rates and 40% of neurons increased firing rates after injection of the calcium antagonist. The latency following On/Off-stimulation was rather constant, whereas the median latency following stimulation with moving light bars increased by about 15O ms after administration of nimodipine. In conclusion, nimodipine alters neuronal response characteristics in the visual cortex of the cat.</p>","PeriodicalId":7035,"journal":{"name":"Acta physiologica et pharmacologica Bulgarica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21216500","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}