31P MR spectroscopy was used to measure the signal intensity ratios of high-energy metabolites for the calculation of free cytosolic magnesium concentration [fMg2+] and pH in the calf muscles of patients with primary juvenile hypertension and of healthy controls. Surface coil and spectroscopic imaging techniques were used. In patients with hypertension, the concentrations of [fMg2+] was 788±33 mmol/l and intracellular pH was 7.05±0.02; these values were not significantly different from the results obtained in healthy controls ([fMg2+], 776±21 mmol/l and pH, 7.06±0.01). Biochemical assays of magnesium in the serum (S-Mg) and in urine (DU-Mg) confirmed this finding. Significant differences in the relative signal intensities of high-energy phosphates between patients with primary juvenile hypertension and healthy controls were observed: a) signal intensity ratios of PCr/Pi, PCr/PbATP, PDE/PbATP were increased, and b) Pi/PDe, Pi/PATP were decreased. The results were the same irrespective of whether the surface coil method or 31P spectroscopic imaging were employed., M. Hájek, D. Palyzová, M. Kořínek, D. Kurková., and Obsahuje bibliografii
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
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
a1_Both divisions of the autonomic nervous system are involved in regulation of urinary bladder function. Several substances, other than noradrenaline and acetylcholine, seem to play important roles in physiology and pathophysiology of lower urinary tract. In the current study, we aimed to examine if there exist interplays between nitric oxide (NO) and autonomic transmitters and if such interactions vary in different parts of the urinary bladder in healthy and cyclophosphamide (CYP)-induced cystitic rats; when administered to the animals (100 mg/kg; i.p.), the cytotoxic CYP metabolite acrolein induces bladder inflammation. In the current study a series of in vitro functional studies were performed on detrusor muscle strip preparations. Stimulation with electrical field stimulation (EFS), methacholine, adenosine 5´-triphosphate (ATP), and adrenaline evoked contractile responses in isolated bladder preparations that were significantly reduced in cyclophosphamide (CYP)-treated rats. While the nitric oxide synthase inhibitor N ω -nitro-L-arginine (L-NNA; 10-4 M) did not affect contractile responses in normal, healthy strip preparations, it significantly increased the contractile responses to EFS, methacholine and adrenaline, but not to ATP, in the bladders from the CYP-treated rats. In the CYP-treated rats, the ATP-evoked relaxatory part of its dual response (an initial contraction followed by a relaxation) was 6-fold increased in comparison with that of normal preparations, whereas the isoprenaline relaxation was halved in the CYP-treated. While L-NNA (10-4 M) had no effect on the isoprenaline-evoked relaxations, it reduced the ATP-evoked relaxations in strip preparations from the bladder body of CYP-treated rats., a2_Stimulation of β2- and β3-adrenoceptors evoked relaxations and both responses were reduced in cystitis, the latter to a larger extent. In the trigone, the reduced ATP-evoked contractile response in the inflamed strips was increased by L-NNA, while L-NNA had no effect on the ATP-evoked relaxations, neither on the relaxations in healthy nor on the larger relaxations in the inflamed trigone. The study shows that both contractile and relaxatory functions are altered in the state of inflammation. The parasympathetic nerve-mediated contractions of the body of the bladder, evoked by the release of ATP and acetylcholine, were substantially reduced in cystitis. The relaxations to β-adrenoceptor and purinoceptor stimulation were also reduced but only the ATPevoked relaxation involved NO., R. Veselá ... [et al.]., and Obsahuje seznam literatury
Hypertension is one of the major risk factor of cardiovascular diseases, but after a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. One reason is that blood pressure is a quantitative trait with multifactorial determination. Numerous genes, environmental factors as well as epigenetic factors should be considered. There is no doubt that although the full manifestation of hypertension and other cardiovascular diseases usually occurs predominantly in adulthood and/or senescence, the roots can be traced back to early ontogeny. The detailed knowledge of the ontogenetic changes occurring in the cardiovascular system of experimental animals during particular critical periods (developmental windows) could help to solve this problem in humans and might facilitate the age-specific prevention of human hypertension. We thus believe that this approach might contribute to the reduction of cardiovascular morbidity among susceptible individuals in the future., J. Kuneš, ... [et al.]., and Obsahuje seznam literatury
Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-α was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-α in all groups. Curcumin significantly ameliorated the ischemiainduced alterations in serum TNF-α and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI., F.T. Hammad, S. Al-Salam, L. Lubbad., and Obsahuje seznam literatury
This study was designed to measure nitrite/nitrate and cytokine levels of serum obtained from septic shock patients and to describe potential depressant effects of human septic serum on rat cardiomyocytes. Serum was prepared from 10 non-septic patients and 10 patients with documented septic shock. Adult rat ventricular myocytes were exposed to 20 % serum in the medium. Cardiomyocyte contractility was assessed by measuring shortening fraction and shortening velocity. Serum levels of nitrite/nitrate, a marker of nitric oxide final metabolites, and cytokines (tumor necrosis factor (TNF)-α, interleukin (IL) 1β , 6, 10, 8 and 12p70) were measured. Compared with serum from non-septic patients, serum of septic shock patients induced rapid reduction of the extent and velocity of shortening in isolated cardiomyocytes. Nitrite/nitrate, TNF-α , IL-1β and IL-12p70 concentrations of tested serum for cardiomyocyte studies were not increased in septic serum compared with controls . In contrast, septic serum that induced a depression of in vitro contractility, had increased levels of IL-6, IL-8 and IL-10. We can conclude that the depression of in vitro contractility induced by septic serum is not directly dependent on elevated levels of nitric oxide metabolites, TNF-α or IL-1β. Our results support the view that other cytokines, including IL-6, IL-8 and IL-10, are potent circulating mediators of myocardial depression in cardiomyocytes., O. Joulin, P. Petillot, M. Labalette, S. Lancel, R. Neviere., and Obsahuje bibliografii a bibliografické odkazy
A rise in baseline cytosolic free Ca2+ in canine vascular endothelial-like cells (VEC) lining the luminal surface of the polyester arterial prosthesis is described. In one, three and six month implantation experiments we employed six adult mongrel dogs, polyester arterial prostheses Arteknit Ra K, fluorescent Ca2+ indicator Fura-2 and digital imaging microscopy to study cytosolic free Ca2+ in cultured VEC. The electron microscopy scanning of the luminal surface in different regions of the graft were also performed. A rise in cytosolic free Ca2+ in the VEC lining the luminal surface of the prosthesis is probably the result of the immunologic reaction and mechanical stress which stimulate the proliferation activity of the endothelial cells. It seems that the baseline cytosolic free Ca2+ reflects the course of the endothelization process on the polyester arterial prosthesis., P. Ondruš, R. Alberty, P. Pothier, V. Echavé, J. Poisson, G. Bkaily., and Obsahuje bibliografii
The use of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ) which is widely used in agriculture is known to cause dopaminergic neurotoxicity. However, the mechanisms underlying this effect are not fully understood. This present study investigated the behavioral manifestations, motor coordination, and dopaminergic neurodegeneration following exposure to PQ. Male rats were injected with PQ (10 mg/kg i.p.) daily for three weeks. Rotarod systems were used for measuring locomotor activity and motor coordination. The effects of PQ on dorsiflexor, electrophysiologically-induced muscle contraction were studied. Dopamine concentrations in the ventral mesencephalon were measured by high performance liquid chromatography and the number of dopaminergic neurons in substantia nigra pars compacta was estimated by tyrosine hydroxylase immunohistochemistry. PQ induced difficulty in movement and significant reduction in motor activity and twitch tension at the dorsiflexor skeletal muscle. The number of tyrosine hydroxylase positive neurons was significantly less in the substantia nigra pars compacta and nigral dopamine level was significantly reduced in PQ treated animals (20.4±3.4 pg/mg) when compared with control animals (55.0±2.4 pg/mg wet tissue). Daily treatment of PQ for three weeks induces selective dopaminergic neuronal loss in the substantia nigra and significant behavioral and peripheral motor deficit effects., M. A. Fahim, ... [et al.]., and Obsahuje seznam literatury