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Biomedical subjects

A Czarnecki

Publications and source records attributed to A Czarnecki.

At least 37 records · Page 2Linked to original sources

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↗

Receptor subtypes for natriuretic peptides in the brains of hypertensive rats.

Receptor subtypes for alpha-atrial natriuretic peptide (alpha-ANP) were characterized in brains of 12-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) by in vitro autoradiography, using des[Gln18, Ser19,Gly20,Leu21,Gly22]ANP-(4-23) (C-ANP) and ANP-(5-25) as subtype-selective ligands. 125I-labeled alpha-ANP (200 pM) bound reversibly to arachnoid mater (AM), choroid plexus (ChP), subfornical organ (SFO), median preoptic nucleus, and supraoptic nucleus. Apparent Kd values for alpha-ANP in AM, ChP, and SFO were 1-6 nM and they were lowest in SHR. Maximal binding capacities for alpha-ANP on ChP and SFO were also significantly lower in SHR, and 10 microM C-ANP or 10 microM ANP-(5-25) inhibited most radioligand binding on AM of WKY and SHR. C-ANP significantly inhibited no other alpha-125I-ANP binding. ANP-(5-25) was a relatively weak inhibitor of alpha-125I-ANP binding to ChP and SFO in WKY but it was powerful in SHR. The results suggest that AM expresses clearance receptor for alpha-ANP in WKY and SHR. Other structures do not express this receptor significantly but express two other receptors for alpha-ANP, one mainly in WKY and one mainly in SHR.

Animals↗

Binding of atrial and brain natriuretic peptides in brains of hypertensive rats.

Displacement of bound [125I]alpha-atrial natriuretic peptide (alpha-ANP) by brain natriuretic peptide (BNP) was used to map receptors common to both peptides in rat brain by in vitro autoradiography. Both spontaneously hypertensive rats (SHR) and the normotensive Wistar-Kyoto control strain (WKY) were studied. In both strains, [125I]alpha-ANP bound densely to subfornical organ, choroid plexus and arachnoid mater. Binding at these sites in either strain was displaced similarly by 1 microM unlabelled alpha-ANP or BNP. However, no [125I]alpha-ANP was displaced by peptides unrelated to alpha-ANP or BNP. In WKY, both alpha-ANP and BNP competed with similarly high affinities for binding sites occupied by [125I]alpha-ANP. This was also true for SHR. However, SHR showed a substantial reduction in the maximum number of binding sites in the subfornical organ and choroid plexus which were competed for by the peptides. Therefore, BNP may be a significant high affinity ligand for brain receptors previously thought specific for atrial natriuretic peptides, including receptors which vary between WKY and SHR.

Animals↗

Autoradiographic localization of atrial and brain natriuretic peptide receptors in rat brain.

Displacement of bound 125I-labeled atrial natriuretic peptide-(1-28) [alpha 125I-ANP-(1-28)] by alpha-ANP-(5-28) and porcine brain natriuretic peptide (BNP) was used to map receptors common to these peptides in rat brain by in vitro autoradiography. alpha-125I-ANP bound reversibly to subfornical organ, area postrema, median preoptic, supraoptic and paraventricular nuclei, and arachnoid mater. Binding at these sites was displaced similarly by 1 microM unlabeled alpha-ANP, alpha-ANP-(5-28), and BNP. Binding dissociation constants in the subfornical organ and arachnoid were 4.40 +/- 1.15 and 3.99 +/- 0.86 nM, respectively, for alpha-ANP, and 2.41 +/- 1.11 and 2.23 +/- 1.06 nM, respectively, for BNP. alpha-125I-ANP also bound to choroid plexus. Here 1 microM unlabeled alpha-ANP displaced significantly more radioligand than did 1 microM BNP, and the concentration displacing 50% of bound radioligand was 2.23 +/- 0.78 nM for alpha-ANP and 1.51 +/- 0.67 nM for BNP. alpha-ANP-(5-28) also displaced alpha 125I-ANP at all sites with significantly greater affinity than did unlabeled alpha-ANP. alpha-125I-ANP was not displaced by completely unrelated peptides. Therefore, both atrial and brain natriuretic peptides may be high-affinity ligands at common receptors in some cerebral localities.

Animals↗

Distribution of atrial natriuretic peptide receptor subtypes in rat brain.

The presence and distribution of atrial natriuretic peptide (ANP) clearance receptors in rat brain were investigated by use of des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-2 3) (C-ANP), a specific ligand of this receptor, to displace bound alpha-125I-labeled ANP. alpha-125I-ANP (200 pM) bound significantly to arachnoid mater, subfornical organ, choroid plexus, area postrema, median preoptic nucleus, and supraoptic and paraventricular nuclei. Binding was reversible at all sites with unlabeled alpha-ANP. Binding dissociation constants for alpha-ANP were measured for the first three sites and were all in the nanomolar range. C-ANP competed with alpha-125I-ANP only for binding sites on arachnoid mater, 1 microM C-ANP displacing radioligand from at least 60% of these sites. No alpha-125I-ANP was displaced by completely unrelated peptides. The reversible binding of 125I-Tyr0-ANP-(5-25), another relatively selective ligand of the clearance receptor, was also concentrated on arachnoid mater. Therefore, high-affinity binding sites for alpha-ANP on arachnoid mater may be clearance receptors for ANP.

Animals↗

Protective effect of inosine on adrenaline-induced myocardial necrosis.

The influence of inosine (200 and 400 mg/kg i.p.) on adrenaline-induced myocardial necrosis in rats was studied. Adrenaline in a single dose (1 and 2 mg/kg s.c.) produced heart cell necrosis estimated by plasma activities of CPK-MB, CPK, blood lactates concentration and histopathological examination. In experimental groups inosine injected simultaneously and 10 minutes after adrenaline evoked significant suppression of CPK-MB and CPK enhancement measured 4 and 24 hours after adrenaline administration. The lower blood lactates concentration 4 hours after adrenaline injection was also found when preceded by inosine. Histopathological examination showed marked protection of the affected myocardium.

Animals↗

The influence of inosine on adriamycin-induced cardiomyopathy in rats.

The effect of inosine on adriamycin-induced cardiomyopathy was studied. Total adriamycin (ADR) dose of 25 mg/kg i.p. injected in 15 equal partial doses 3 times a week for five following weeks evoked fully developed cardiomyopathy in rats. Inosine 200 mg/kg i.p. injected 5 times a week parallel to ADR diminished ADR cardiotoxicity evaluated by electrocardiographic recordings and histopathological examination. Moreover lower cytostatic toxicity was observed as judged by less-expressed leucopenia and lower SGOT activities in inosine treated animals.

Animals↗

The surgeon's mental load during decision making at various stages of operations.

In surgeons while opening the wound, during the operation proper, closing the skin and immediately after the operation, the ECG was recorded telemetrically for 5-min periods. From the ECG recordings, indices reflecting cardiac arrhythmia and emotional level were calculated. It is concluded that the process of decision making during the vital stages of operations causes a fall in the CHRV (the coefficient of heart rate variability), S2 (the variance of R-R intervals) and VR (the variability range of R-R intervals). It seems that of the indices studied, the most suitable for evaluation of the degree of mental loading due to decision making processes are the CHRV and S2. During all the stages of surgery studied, and immediately after the operation, an increase in tonus of the sympathetic nervous system occurs in surgeons indicating a rise in emotional level.

Arrhythmias, Cardiac↗

Haemodynamic effects of inosine. A new drug for failing human heart?

Haemodynamic effects of inosine were studied in intact dogs and subsequently in patients suffering from prolonged otherwise intractable cardiogenic shock. The nucleoside significantly improve myocardial performance in patients with an extremely low cardiac index by 63 +/- 29% as well as animals with no signs of haemodynamic deterioration, increasing cardiac output by 12.2 +/- 4.3%. These results suggest that inosine may become a promising inotropic agent. Further studies though are necessary to elucidate the mechanism of inosine action.

Adult↗