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Introduction Peristaltic activity of ureteral smooth muscle propels urine from the kidneys to the urinary bladder. The muscular layer within the wall of the ureter comprises both circular and longitudinal layers of smooth

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Circumferential stretch due to increases in pressure induces vascular smooth muscle cell depolarization and contraction known as the myogenic response. The aim of this study was to determine the in vivoeffects of axial-longitudinal stretch of the rat saphenous artery (SA) on smooth muscle membrane potential (Em) and on external diameter. Consecutive elongations of the SA were carried out from resting length (L0) in 10% increments up to 140% L0while changes in membrane potential and diameter were determined in intact and de-endothelized vessels. Axial stretching resulted in a small initial depolarization at 120% of L0followed by a progressive 20 to 33% hyperpolarizaion of vascular smooth muscle between 130% and 140% of L0. At 140%, an average maximal 10.6 mV reversible hyperpolarization was measured compared to –41.2±0.49 mV Em at 100% L0. De-endothelialization completely eliminated the hyperpolarization to axial stretching and augmented the reduction of diameter beyond 120% L0. These results indicate that arteries have a mechanism to protect them from vasospasm that could otherwise occur with movements of the extremities.

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Acta Physiologica Hungarica
Authors:
Zorana Oreščanin-Dušić
,
Č. Miljević
,
M. Slavić
,
A. Nikolić-Kokić
,
D. Blagojević
,
D. Lečić-Toševski
, and
M. Spasić

Tianeptine is a novel anti-depressant with an efficacy equivalent to that of classical anti-depressants. Additional beneficial effects include neuroprotection, anti-stress and anti-ulcer properties whose molecular mechanisms are still not completely understood but may involve changes in the anti-oxidant defence system. Herein, we have studied the effects of tianeptine on both contractile activity of isolated rat uteri and components of the endogenous anti-oxidative defence system. Tianeptine-induced dose-dependent inhibition of both spontaneous and Ca2+-induced contraction of uterine smooth muscle. The effect was more pronounced in the latter. Tianeptine treatment increased glutathioneperoxidase (GSH-Px) and catalase (CAT) activities in spontaneous and Ca2+-stimulated uteri. A significant decrease in glutathione-reductase (GR) activity in both spontaneous and Ca2+-induced uterine contractions after tianeptine treatment indicated a reduction in reduced glutathione and consequently a shift toward a more oxidised state in the treated uteri. In spontaneously contracting uteri, tianeptine caused a decrease in copper-zinc SOD (CuZnSOD) activity. Tianeptine’s anti-depressant effects may be accomplished by triggering a cascade of cellular adaptations including inhibition of smooth muscle contractility and an adequate anti-oxidative protection response.

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. Barthó , L. , Benkó , R. , Patacchini , R. , Pethő , G. , Holzer-Petsche , U. , Holzer , P. , Lazar , Z. , Undi , S. , Illenyi , L. , Antal , A. , Horváth, Ö. P. ( 2004 ) Effects of capsaicin on visceral smooth muscle: a valuable

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The significance of autonomic nerves reaching the pineal organ was already investigated in connection to the innervation of pinealocytes and mediating light information from the retina for periodic melatonin secretion. In earlier works we found that some autonomic nerve fibers are not secretomotor but terminate on arteriolar smooth muscle cells in the pineal organ of the mink (Mustela vison). Studying in serial sections the pineal organ of the mink and 15 other mammalian species in the present work, we investigated whether similar axons of vasomotor-type are generally present in the wall of pineal vessels, further, whether they reach the organ via the conarian nerves or via periarterial plexuses. In all species investigated, axons of perivasal nerve bundles were found to form terminal enlargements on the smooth muscle layer of pineal arterioles. The neuromuscular endings contain several synaptic and some granular vesicles. Axon terminals are also present around pineal veins. In serial sections, we found that the so-called conarian autonomic nerves reach the pineal organ alongside pineal veins draining into the great internal cerebral vein. Similar nerves present near arteries of the arachnoid enter the pineal meningeal capsule and septa by arterioles, both perivenous and periarterial nerves form terminals of vasomotor-type. The arteriomotor and venomotor regulation of the tone of the vessels of the pineal organ may serve the vascular support for circadian and circannual periodic changes in metabolic activity of the pineal tissue.

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Human cytomegalovirus (HCMV) infection may be involved in the pathogenesis of atherosclerosis by modulating functions of smooth muscle cells (SMC). In this study, we performed an oligonucleotide microarray screening of 780 inflammation-associated genes in HCMV-infected aortic SMC (AoSMC). The expression of 31 genes was stimulated and 24 genes were down-regulated following infection with HCMV strain DC-134. Following infection with HCMV strain AD-169 infection, we found 24 genes to be stimulated and 32 genes to be down-regulated. Among these were primarily genes encoding for CC and CXC chemokines, adhesion molecules, and tumor necrosis factor (TNF) receptor superfamily members, apoptosis-related factors, signal transduction molecules and transcription regulators. The up-regulated genes included matrix metalloproteinase (MMP)-1 and MMP-3 in HCMV infected cells. Using RT-PCR and enzyme immunoassay we found stimulated expression of MMP-1 (3.2-fold expression) and MMP-3 (334-fold expression) in HCMV strain DC-134-infected AoSMC at 72 h following infection.The findings of our study suggest that HCMV infection of AoSMC cause an activation of atherosclerosis-relevant factors in SMC. The increased expression of MMPs which have been shown to be involved in atherosclerotic plaque rupture and myocardial infarction is in agreement with the hypothesis that this pathogen might contribute to plaque inflammation in atherosclerotic disease.

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Microorganisms such as Chlamydia pneumoniae have been shown to infect vascular cells and are believed to contribute to vascular inflammation and atherosclerotic plaque development. Plasma levels of oxidized low density lipoprotein (oxLDL) have received considerable attention as potential predictors of prognosis in atherosclerotic diseases. Lectin-like oxidized LDL receptor-1 (LOX-1) is one of the major receptors for oxidized LDL. It was investigated whether C. pneumoniae infection can stimulate expression of LOX-1 in vascular smooth muscle cells. Expression of LOX-1 in VSMC was measured by RT-PCR and immunoblotting following C. pneumoniae infection. To examine the pharmacological effect of a HMG-CoA reductase inhibitor on LOX-1 expression, cells were co-incubated with fluvastatin immediately after infection. Adose and time dependent expression of LOX-1mRNAand protein was found in C. pneumoniae infected SMC. After heat and UV light treatment of the chlamydial inoculum the level of LOX-1 was reduced to that of mock-infected cultures. Furthermore, treatment of infected cells with fluvastatin decreased LOX-1 expression to baseline levels. The up-regulation of LOX-1 induced by C. pneumoniae could lead to continued lipid accumulation in atherosclerotic lesions. Together with the widespread expression of LOX-1, this might contribute to the epidemiologic link between C. pneumoniae infection and atherosclerosis. The effect of lowering the LOX-1 expression by fluvastatin may provide a pharmacological option of limiting oxLDL uptake via its scavenger receptor.

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Acta Physiologica Hungarica
Authors:
Z. Oreščanin-Dušić
,
Č. Miljević
,
M. Slavić
,
A. Nikolić-Kokić
,
R. Paskulin
,
D Blagojević
,
D. Lečić-Toševski
, and
M. Spasić
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Contraction of ureteral smooth muscle drives the urine bolus to the urinary bladder for storage prior to micturition. This study describes a novel approach to the measurement of ureteral pressure generation in vitro and the influence of distending pressure on acetylcholine-stimulated ureteral lumenal pressure generation.Isolated segments of ureters obtained from Wistar rats were pressurised in a blind-ended sac arrangement and contractile responses were recorded as phasic oscillations in ureteral luminal pressure. Distal segments generated greater luminal pressures than proximal segments (p<0.001) in response to acetylcholine. Increasing baseline distending pressures in the range 2–10 mmHg in proximal segments was associated with greater frequency of contraction (p<0.001) and decreased magnitude of contraction (p<0.001) when expressed as % maximum response. Nifedipine (10 −5 M) or removal of extracellular Ca 2+ abolished the contractions. Isometric contractile responses of ureteral ring preparations were not significantly influenced by pretensions equivalent to distending pressures in the range 2–10 mmHg.This is the first study to fully establish the influence of baseline ureteral distending pressure upon ureteral luminal pressure generation in vitro and demonstrates regional heterogeneity of ureteral contractile responses. It is suggested that this experimental approach may be a useful methodology for the investigation of ureteral function during urinary outflow obstruction.

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Bradykinin (BK) and related kinins are autocoid peptides that play integral roles in many pathophysiological processes such as cough. In this study, the inhibitory effect of noscapine, the antitussive opioid alkaloid, on BK receptors, was tested in the guinea-pig ileum. Contractions of the isolated ileum of the guinea-pig in response to BK were inhibited by noscapine (10–1000 nM) in a concentration-dependent manner. Concentration-response curves (CRCs) to BK were slightly shifted to the right with a concomitant decrease in the maximum effect. A pA2value of 6.68 was calculated for noscapine. The slope of the Schild plot of the antagonism was found to be 0.56. Noscapine had no effect on contractions induced by KCl, acetylcholine, histamine,5-hydroxy tryptamine or angiotensin II. In conclusion, noscapine has a specific antagonistic effect on BK receptors and the mode of inhibition was found to be non-competitive.

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