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322. Connexin 43 expression in human hypertrophied heart due to pressure and volume overload
- Creator:
- Vetter, C., Zweifel, M., Zuppinger, C., Carrel, T., Martin, D., Haefliger, J.-A., and Delacrétaz, E.
- Format:
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, fyziologie člověka, srdce, human physiology, heart, gap junction, connexin43, cardiac hypertrophy, aortic stenosis, remodeling, 14, and 612
- Language:
- English
- Description:
- Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution., C. Vetter ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
323. Connexin 50 mutation lowers blood pressure in spontaneously hypertensive rat
- Creator:
- Ondřej Šeda, František Liška, Michal Pravenec, Zdenka Vernerová, Ludmila Kazdová, Drahomíra Křenová, Václav Zídek, Lucie Šedová, Michaela Krupková, and Vladimír Křen
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- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, hypertenze, inzulinová rezistence, hypertension, insulin resistance, connexin, transcriptome, animal models, 14, and 612
- Language:
- English
- Description:
- We assessed the effect of the previously uncovered gap junctio n protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR - Dca ) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR - Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR - Dca compared with SHR (P<0.01 and P<0.05 , respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR - Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basa l insulin sensitivity in muscle. There were 21 transc ripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR - Dca. Tumor necrosis factor was the most significant upstream regulato r and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR - Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR - Dca strain, decr eases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney., O. Šeda, F. Liška, M. Pravenec, Z. Vernerová, L. Kazdová, D. Křenová, V. Zídek, L. Šedová, M. Krupková, V. Křen., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
324. Constitutive Inhibitory Action of Muscarinic Receptors on Adenylyl Cyclase in Cardiac Membranes and Its Stereospecific Suppression by Hyoscyamine
- Creator:
- Jan Říčný, Gualtieri, F., and Stanislav Tuček
- Format:
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- Type:
- article, studie, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, fyziologie člověka, human physiology, Muscarinic receptors, Adenylyl cyclase, Constitutive activity of receptors, Hyoscyamine, Atropine, Heart, Inverse agonist action, 14, and 612
- Language:
- English
- Description:
- Muscarinic acetylcholine receptors in the heart have been shown to display agonist-independent spontaneous (constitutive) activity which causes changes in the opening of cardiac ion channels and in the activity of G proteins. We investigated whether an inhibition of the constitutive activity of muscarinic receptors induced by the binding of antagonist brings about a change in the synthesis of cyclic AMP in rat cardiac membranes, and whether the action of the antagonist is stereospecific. Atropine and S-(-)-hyoscyamine were indeed found to enhance the forskolin-stimulated synthesis of cyclic AMP in rat cardiac (both atrial and ventricular) membranes by up to 24%. The effect was stereospecific and the potency of R-(+)-hyoscyamine was 30 fold lower than that of the S-(-) enantiomer, confirming that the action of hyoscyamine is receptor-mediated. The effect did not depend on the presence of endogenous acetylcholine in the system used. The results strongly suggest that the adenylyl cyclase in the heart is exposed to continuous mild inhibition by constitutively active muscarinic receptors in the membranes of cardiomyocytes., J. Říčný, F. Gualtieri, S. Tuček., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
325. Contemporary activation of different endothelial receptors accounts for a reserve mechanism of nitric oxide-mediated relaxation
- Creator:
- Kyselá, S. and Török, J.
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- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, relaxace, acetylcholin, histamin, adenosin, oxid dusnatý, relaxation, acetylcholine, histamine, adenosine, nitric oxide, pulmonary artery, clonidine, 14, and 612
- Language:
- English
- Description:
- The aim of this study was to investigate whether the inhibition of one of the endothelial receptor sites in the rat pulmonary artery (muscarinic, histaminergic, purinergic, a 2-adrenergic) affects the NO-mediated relaxation induced by the activation of the other type of receptors. Acetylcholine (ACh)-, histamine (Hist)-, adenosine (Ade)- , and clonidine (Clon)-induced endothelium-dependent relaxations were reduced by the administration of specific antagonists of muscarinic, H1-histaminergic, purinergic or a 2-adrenergic receptors, respectively. The inhibition of H1-histaminergic receptors by chlorphenyramine did not prevent ACh-induced relaxation. Similarly, the inhibition of muscarinic receptors by atropine did not prevent the relaxations to histamine, adenosine and clonidine. On the other hand, the relaxations induced by acetylcholine, histamine, adenosine or clonidine were regularly reduced by NO-synthase inhibitor NG-nitro-L-arginine methyl ester (10-4 mol/l). These results suggest that the inhibition of NO-synthase abolished arterial relaxations induced by all agonists. After inhibition of one type of the endothelial receptors, the NO-dependent relaxation could still be evoked by activation of one of the others., S. Kyselá, J. Török., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
326. Contractile effects of endothelins on isolated human ureter
- Creator:
- Jankovic, S. M., Jankovic, S. V., Stojanovic, V., Stojadinovic, D., Stojadinovic, M., Canovic, D., and Stefanovic, S.
- Format:
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, hladké svaly, smooth muscles, endothelins, human ureter, intraluminal pressure, 14, and 612
- Language:
- English
- Description:
- The aim of our study was to inve stigate mechanism of action of endothelins 1, 2 and 3 on spontaneous activity, tone and intraluminal pressure of human ureter. Both longitudinal tension and intraluminal pressure were recorded from the isolated segments of proximal human ureter. Endothelins 1, 2 and 3 (5.35x10 -11 M- 5.05x10-8M) produced concentration-dependent tonic contraction and sustained increase in intraluminal pressure of isolated preparations of hum an ureter. Endo thelins 1 and 3 produced also concentration-dependent inhibition of spontaneous, phasic contractions of the isolated preparations. Selective antagonist of ETA receptors BQ123 and selective antagonist of ET B receptors BQ788 produced significant inhibition of endothelin-1-induced tonic contraction (pA2=8.80 and 6.55, respectively) and increase in intraluminal pressure (pA2=8.68 and 7.02, respectively), while they did not affect endothelin-1-induced inhibition of spontaneous activity. Endothelin 1 produces increase in tone and intraluminal pressure of isolated human ureter acting on both ETA and ETB receptors, the first one being functionally more important. On ly endothelins 1 and 3 inhibit spontaneous, phasic activity of human ureter, but this effect was not blocked by selective antagonists of ETA and ETB receptors., S. M. Jankovic ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
327. Contribution of ABCB1 and CYP2D6 genotypes to the outcome of tamoxifen adjuvant treatment in premenopausal women with breast cancer
- Creator:
- Soňa Argalácsová, Ondřej Slanař, Pavel Vítek, Petra Tesařová, Bakhouche, H., Marcela Dražďáková, Bartošová, O., Tomáš Zima, and Luboš Petruželka
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- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, farmakogenomika, pharmacogenomics, p-glycoprotein, SNP, tamoxifen, CYP2D6, 14, and 612
- Language:
- English
- Description:
- Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity., S. Argalácsová, O. Slanař, P. Vítek, P. Tesařová, H. Bakhouche, M. Dražďáková, O. Bartošová, T. Zima, L. Pertuželka., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
328. Contribution of captopril thiol group to the prevention of spontaneous hypertension
- Creator:
- Oľga Pecháňová
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- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, hypertenze, thioly, hypertension, thiols, spontaneous hypertension, captopril, enalapril, nitric oxide synthase, reactive oxygen species, 14, and 612
- Language:
- English
- Description:
- We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121±5 mmHg) was significantly lower than that in the enalapril group (140±5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration., O. Pecháňová., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
329. Contribution to the V-V interval optimizaton in patients with cardiac resynchronization therapy
- Creator:
- Miroslav Novák, Jolana Lipoldová, Jaroslav Meluzín, Krejčí, J., Petr Hude, Věra Feitová, Ladislav Dušek, Pavel Kamarýt, and Jiří Vítovec
- Format:
- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, kardiologie, angiologie, cardiology, angiology, biventricular pacing, inter-ventricular asynchrony, intra-ventricular asynchrony, V-V interval, cardic resynchronization therapy, 14, and 612
- Language:
- English
- Description:
- The present study proposed procedure for predicting an optimal left and right ventricular pacing interval delay (V-V interval). In 16 patients (heart failure, left bundle branch block, biventricular pacing) two methods (A and B) identifying optimal V-V interval were tested. Method A: predicted optimal V-V interval A (POVV-A) = electromechanical delay of the segment paced by left ventricle lead minus electromechanical delay of the segment paced by right ventricle lead. Method B: predicted optimal V-V interval B (POVV-B) = difference in the onset of aortic and pulmonary flows. Both methods were validated using echocardiography and right-sided heart catheterization. Cardiac output during POVV-A (4.6 l.min-1 ) was significantly better than that during POVV-A minus 20 ms (4.3 l.min-1, p<0.01) and POVV-A plus 20 ms (4.3 l.min-1 , p<0.01), and than that during POVV-B (4.4 l.min-1, p<0.05). LV dP/dt during POVV-A (818 mm Hg.s-1 ) exceeded that during POVV-A plus 20 ms (717 mm Hg.s-1 , p<0.05) and POVV-A minus 20 ms (681 mm Hg.s-1, p<0.05), and that during POVV-B (727 mm Hg.s-1 , p<0.01). The time difference in onsets of myocardial deformation of left ventricle segment paced by the left ventricle and right ventricle lead allows identifying the optimal V-V interval and improves left ventricle performance., M. Novák, J. Lipoldová, J. Meluzín, J. Krejčí, P. Hude, V. Feitová, L. Dušek, P. Kamarýt, J. Vítovec., and Obsahuje bibliografii a bibliografické odkazy
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
330. Control of breathing and brain activation in human subjects seen by functional magnetic resonance imaging
- Creator:
- Václav Šmejkal, Rastislav Druga, and Jaroslav Tintěra
- Format:
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- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, magnetická rezonance, magnetic resonance (physics), respiratory control, brain activation, 14, and 612
- Language:
- English
- Description:
- Functional magnetic resonance imaging (fMRI) was used to demonstrate the brain activation during transition from unconscious to conscious breathing in seven healthy human subjects. In right-handed volunteers, the activated areas were found in both hemispheres. The medial part of the precentral gyrus (area 4) was constantly activated in the left hemisphere. Additional activated areas were demonstrated in the premotor cortex and in the posterior parietal cortex. The activated cortical sites exhibited analogous distribution in the right hemisphere. In two out of the seven subjects, activated sites were also observed in the cerebellar hemispheres, and in the lentiform and caudate nuclei., V. Šmejkal, R. Druga, J. Tintěra., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public