The function of chromogranin A (CGA) is reviewed, and the radioimmunometric determination of plasma CGA was evaluated as a marker of pheochromocytoma using a comparison of pheochromocytoma patients immediately before surgery (group P, n=25, 635±451 ng/ml) with other groups of patients, i.e. pheochromocytoma patients approximately 1 year after removal of tumor (group PP, n=13, 69±33 ng/ml), medullary thyroid carcinoma patients (group M, n=22, 106±59 ng/ml), congenital adrenal hyperplasy patients (n=33, 65±40 ng/ml), and controls (n=31, 66±29 ng/ml). A CGA level above cut off value 130 ng/ml was found in 24 of 25 patients in group P, 1 (relapse) of 13 patients in group PP, and 4 of 22 patients in group M. In the group P we found a significant association between the size of the tumors removed and plasma CGA concentrations (p=0.0016), and also a significant (p=0.0016) relationship between plasma CGA concentrations and PASS score rating the malignity of pheochromocytoma. We can conclude that plasma CGA concentration as determined by radioimmunometric assay (which is simple without the necessity of special laboratory equipment) is an effective marker of pheochromocytoma with association to malignity and tumor mass., R. Bílek, L. Šafařík, V. Ciprová, P. Vlček, L. Lisá., and Obsahuje bibliografii a bibliografické odkazy
Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178±14 μm and 171±9 μm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was higher (16.5±1.9 % vs. 12.9±0.9 %), which resulted in a reduced lumen size (144±9 μm vs. 167±12 μm), thicker vascular wall (22.6±1.8 μm vs. 17.4±1.6 μm) and decreased tangential wall stress (16.8±1.1 kPa vs. 20.5±1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01 in all these comparisons). Elevated basal NO release resulted in increased endothelial dilation in quercetin-treated animals, especially at higher intraluminal pressures (10.8±2.5 % vs. 5.7±1.3 % at 70 mm Hg, p<0.01). We found remodeling of the geometry of coronary arterioles to ensure higher dilatory reserve and nitrogen monoxide production, as well as lowered elastic stress of the vessel wall., A. Monori-Kiss, F. Kiss, J. M. Restifo, E. Monos, G. L. Nadasy., and Obsahuje bibliografii
We aimed to compare the effects of chronic and acute administration of structurally different antihypertensives, diuretics - indapamide and hydrochlorothiazide, ACE inhibitor - captopril and indapamide+captopril combination on endothelium-dependent relaxation of femoral artery isolated from nitric oxide (NO)-deficient rats. In the chronic experiment, femoral artery was isolated from Wistar rats receiving L-NAME (40 mg/kg/day) solely or with indapamide (1 mg/kg/day), hydrochlorothiazide (10 mg/kg/day), captopril (10 mg/kg/day), and indapamide+captopril combination for seven weeks. In the acute in vitro experiment, the incubation medium with femoral artery isolated from L-NAMEhypertensive rats was supplemented with investigated antihypertensives in the same concentration 10-4 mol/l. Interestingly, chronic L-NAME treatment did not cause a reduction of vasorelaxation. Indapamide+captopril elevated relaxation above the control level and completely prevented blood pressure increase induced by L-NAME. Acute incubation with captopril only or indapamide+captopril improved relaxation of femoral artery isolated from L-NAMEhypertensive rats, while the incubation with all antihypertensives increased vasorelaxation of femoral artery isolated from control Wistar rats. In conclusion, NO might be involved in the indapamide- and hydrochlorothiazide-induced improvement of vasorelaxation, while different vasorelaxing factors (prostacyclin, EDHF) contribute to the captoprilinduced improvement of vasorelaxation. During the chronic treatment additive and synergic effects of indapamide and captopril may contribute to the prevention of hypertension and increase of vasorelaxation., M. Sládková, S. Kojšová, L. Jendeková, O. Pecháňová., and Obsahuje bibliografii
Vasoactive intestinal polypeptide (VIP) is implicated in the modulation of vagal effects on the heart rate. In this study, the impact of acute and chronic atropine administration on VIP levels in rat heart atria was investigated in relation to heart rate in the course of vagus nerves stimulation. Anaesthetised control and atropinised (10 mg/kg/day for 10 days) rats pretreated with metipranolol and phentolamine that were either given or not a single dose of atropine were subjected to bilateral vagus nerve stimulation (30 min: 0.7 mA, 20 Hz, 0.2 ms). VIP concentrations in the atria were determined afte reach stimulation protocol. In control rats with or without single atropine administration, the heart rate upon vagal stimulation was higher than in atropinised animals with or without single atropine dose, respectively. VIP concentrations in the control atria were significantly decreased after the stimulation; the decrease was comparable both in the absence and presence of a single dose of atropine. Compared to controls, VIP levels were significantly decreased after chronic atropine treatment and they were not further reduced by vagal stimulation and single atropine administration. Administration of VIP antagonist completely abolished the differences in the heart rate upon vagal stimulation between control and atropinised groups. In conclusion, the data indicate that chronic atropine administration affects VIP synthesis in rat heart atria and consequently it modifies the heart rate regulation., J. Kuncová, Š. Faitová, J. Capouch, M. Štengl, J. Slavíková., and Obsahuje bibliografii a bibliografické odkazy
The mechanisms and myocardial alterations associated with NO-deficient hypertension are still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to examine the influence of captopril treatment. Wistar rats were administered either L-NAME (40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4 weeks. A significant increase of blood pressure confirmed the reliability of the model. The results showed that long-lasting L-NAME administration was accompanied by a decrease of endothelial NO-synthase activity and by a significant local decrease of the following enzyme activities: capillary-related alkaline phosphatase, 5’-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase, succinic dehydrogenase, ß-hydroxybutyrate dehydrogenase and ATPases. No activity of these enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical changes correlated with subcellular changes, which were characterized by 1) apparent fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of capillaries as well as by induction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic disturbances and ultrastructural alterations of the heart and these changes are probably not induced by the renin-angiotensin system only., N. Tribulová, Ľ. Okruhlicová, I. Bernátová, O. Pecháňová., and Obsahuje bibliografii
Young castrated male goats (n = 8) were used to investigate the effect of long-term treatment with recombinant methionyl bovine somatotropin in a sustained release vehicle (bST; 100 mg at seven-day intervals in a 147-day experiment) and chronic culture (24 h) of omental adipose tissue in the presence of various hormones on lipogenic responses to catecholamines during acute incubation (2 h) in a sodium acetate supplemented glucose-free buffer. The rate of fatty acid synthesis in freshly-prepared adipose explants was low and did not differ from those cultured in the absence of hormones for 24 h. Hormonal combination of insulin (17 nmol.l-1) plus cortisol (138 nmol.l-1) or insulin plus recombinant enterokinase linker bST (4.5 nmol.l-1) increased lipogenesis (P<0.05). Further addition of bST or cortisol decreased lipogenesis significantly (P<0.05) in the controls but not significantly in bST-treated animals. Cultured explants from either control or bST-treated animals showed significant inhibition of lipogenesis by both norepinephrine (10 m mol.l-1) and isoprenaline (10 m mol.l-1). BST treatment in vivo did not increase the responsiveness of cultured explants to norepinephrine in vitro, however, the responsiveness to isoprenaline(inhibition of lipogenesis) was greater in bST-treated animals than in the controls., J. Škarda., and Obsahuje bibliografii
NG-nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The aim of this study was to investigate the effect of chronic low-dose administration of L-NAME on NO production, vascular function and structure of the heart and selected arteries of rats. Adult male Wistar rats were treated with L-NAME in the dose of approximately 1.5 mg/kg/day in drinking water for 8 weeks. Basal blood pressure (BP) of rats (determined by tail-cuff) was 112±3 mm Hg. The low-dose administration of L-NAME significantly elevated BP measured on the third and sixth week of treatment vs. controls by approximately 9 % and 12 %, respectively. After this period, BP of L-NAME-treated rats returned to the control values. The relative left ventricular mass, heart fibrosis and collagen III/collagen I ratio were not affected by L-NAME. Similarly, there were no alterations in the cross-sectional area and wall thickness/diameter ratio of the aorta and the femoral artery of LNAME- treated rats. NO synthase activity (determined by conversion of [3H]-L-arginine to [3H]-L-citrulline) was not altered in the hypothalamus of L-NAME-treated rats. Interestingly, chronic low-dose L-NAME treatment significantly elevated NO synthase activity in the left ventricle and aorta, increased endothelium-dependent acetylcholine-induced vasorelaxation and reduced serotonin-induced vasoconstriction of the femoral artery. The data suggest that chronic lowdose L-NAME treatment can increase NO production and vasorelaxation in normotensive rats without negative structural changes in the cardiovascular system., I. Bernátová, J. Kopincová, A. Púzserová, P. Janega, P. Babál., and Obsahuje bibliografii
The aim of this study was to analyze the effects of chronic administration of the β-adrenoceptor agonist clenbuterol (2 mg/kg body weight/day for a period of 30 days) on the major contractile protein (myosin) in the left ventricular muscle of the adult mouse heart. Separation of myosin heavy chain (MHC) isoforms on 7.5 % glycerol SDS-PAGE and subsequent quantification of the gels by laser densitometry showed a 6.5-fold increase in the β-isoform of MHC in the clenbuterol-treated group. The α: β ratio of these two isoforms in the control group was 98.16±0.14 %: 1.83±0.14 %, whereas in the treated group it was 88.05±1.15 %: 11.95±1.15 %. Actomyosin ATPase activity assay demonstrated a significant (20 %) decline in ATPase activity of the tissue in the β-agonist-treated group. These results suggest that chronic clenbuterol treatment is capable to induced the transformation of MHC isoforms increasing the slow β-MHC isoform, which may contribute to the altered contractile mechanics of clenbuterol-treated hearts., S. N. Patiyal, S. Sharma., and Obsahuje bibliografii a bibliografické odkazy
Clinical reports suggest close interactions between stressors, particularly those of long duration, and liver diseases, such as hepatic inflammation, that is proposed to occur via reactive oxygen species. In the present study we have used 21-day social isolation of male Wistar rats as a model of chronic stress to investigate protein expression/activity of liver antioxidant enzymes: superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR), and protein expression of their upstream regulators: glucocorticoid receptor (GR) and nuclear factor kappa B (NFkB). We have also characterized these parameters in either naive or chronically stressed animals that were challenged by 30-min acute immobilization. We found that chronic isolation caused decrease in serum corticosterone (CORT) and blood glucose (GLU), increase in NFkB signaling, and disproportion between CuZnSOD, peroxidases (CAT, GPx) and GLR, thus promoting H2O2 accumulation and prooxidative state in liver. The overall results suggested that chronic stress exaggerated responsiveness to subsequent stressor at the level of CORT and GLU, and potentiated GLR response, but compromised the restoration of oxido-reductive balance due to irreversible alterations in MnSOD and GPx., J. Djordjevic ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Stress serves as a risk factor in the etiology of hypertension. The present study was designed to decipher the effect and mechanism of chronic stress on the progression of pressure overload-induced cardiac dysfunction. We used abdominal aortic constriction (AAC) to induce pressure overload with or without chronic restraint stress to establish the animal models. Echocardiographic analysis showed pressure overload-induced cardiac dysfunction was worsened by chronic stress. Compared with the AAC rats, there is a significant increase in cardiac hypertrophy, injury, apoptosis and fibrosis of the AAC + stress rats. Furthermore, we found the secretion of norepinephrine (NE) increased after the AAC operation, while the level of NE was higher in the AAC + stress group. Cardiomyocytes and cardiac fibroblasts isolated from neonatal rats were cultured and separately treated with 1, 10, 100 μM NE. The higher concentration NE induced more cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression. These results revealed that high level of NE-induced cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression further contributes to the effect of chronic stress on acceleration of pressure overloadinduced cardiac dysfunction., W. Liu, X. Wang, Z. Mei, J. Gong, X. Gao, Y. Zhao, J. Ma, F. Xie, L. Qian., and Obsahuje bibliografii