[Centenary of the foundation of the first Association for Physiological Sciences in Hungary].
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Biomedical subjects
Publications and source records attributed to E Monos.
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Physiological functions of the veins include: 1. Blood collectors with flow-rectifying valves; 2. Selective barrier function, venular reabsorption of fluid; 3. Capacity function and redistribution of the blood volume, pressure-damping; 4. Maintaining the filling pressure of the heart by adequate venous return at varying cardiac output; 5. Increasing orthostatic tolerance of the body; 6. Postcapillary resistance; 7. Angiogenesis (in venous side of the microcirculation); 8. Secretion of bioactive substances by the endothelial and smooth muscle cells; 9. Lymphocyte homing (high-endothelial venules); 10. Cooperation between venular endothelium and the polymorphonuclear leukocytes (margination and rolling); 11. Enhanced inhibition of platelet aggregation and thromboembolic reactions; 12. Other special functions (e.g. facial vein: contribution to cranial thermoregulation; internal jugular vein: antisiphonage "device", etc.). Recent results suggest: 1. that intrinsic biomechanical adaptation of the systemic vein wall may occur in response a) to fast pressure changes within the physiological range by myogenic capacity autoregulation of the lumen; b) to long-term physiological haemodynamic loading by increase in total capacity and in short-term myogenic autoregulation range without marked changes of the wall thickness; c) to chronic arterialization with compensatory increase in wall-thickness reducing the extreme mechanical stresses induced by arterial pressure (such changes also imply fibrotic transformation of the wall-structure); 2. EDRF physiologically released by venous endothelium seems to be an important factor protecting the veins against non-desirable increases of smooth muscle tone (e.g. at low Mg-ion level of extracellular fluid, or in case of axial overstretch of the vein, etc.).
Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In noradrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5 x 10(-6) M), and in vessels without endothelium, lowering the magnesium concentration caused a dose-dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)
To reveal a potential modulating effect of vasoactive pharmacological agents on the prostanoid production of the venous wall, prostacyclin and thromboxane release from venous tissue slices was studied. Aortic and caval vein samples from 20 rats as well as from 21 cats were studied. Prostacyclin and thromboxane productions were determined by radioimmunoassay as 6-keto-PGF1 alpha and TxB2 released into the incubation medium. Venous tissue produced significantly less prostacyclin per unit weight than arterial tissue in rats (30.7 +/- 4.6 vs. 52.1 +/- 8.2 pg/mg/min), while in cats an opposite situation was found (16.6 +/- 3.2 vs. 7.06 +/- 1.9 pg/mg/min). Thromboxane production of venous tissue was consequently higher than corresponding values for aortic tissue (3.72 +/- 0.46 vs. 1.54 +/- 0.14 in rats and 3.4 +/- 0.6 vs. 1.33 +/- 0.19 in cats, all values in pg/mg/min). Norepinephrine and dopamine significantly increased both the prostacyclin and the thromboxane release from venous tissue, while isoproterenol had no effect. Vasopressin significantly increased thromboxane release and decreased the ratio of prostacyclin vs. thromboxane production (from 10.4 +/- 1.6 to 7.5 +/- 1.6, in acetylsalicylic acid pretreated cats). Angiotensin and thrombin had no significant effects. Bradykinin (0.5 microgram/ml) significantly augmented prostacyclin release from venous tissue (14.4 +/- 2.6 from 10.9 +/- 2.4 pg/mg/min) and decreased thromboxane release (0.65 +/- 0.18 from 1.35 +/- 0.22 pg/mg/min). Methionine-enkephalin (5 micrograms/ml) significantly reduced the thromboxane release from venous tissue slices. The presented material demonstrates that several vasoactive agents modulate the vasoactive prostanoid release of the venous wall. In some cases, the prostacyclin and the thromboxane productions are influenced separately, which in turn will have its impact on smooth muscle activity and thrombocyte aggregation.
Active and passive mechanical properties of human saphenous and canine femoral and saphenous vein segments were measured in vitro to assess the degree of pressure-dependent venous myogenic tone (% change in diameter, physiological saline solution vs. Ca(2+)-free solution) in these vessels. Stepwise elevation of intraluminal pressure from 2 to 20 mmHg caused an active myogenic response, which was calcium dependent. Side branches of human saphenous veins (OD at 20 mmHg: 1.92 +/- 0.15 mm control; 2.41 +/- 0.18 mm relaxed) displayed a larger degree of myogenic tone (approximately 25%) compared with dog saphenous (OD: 2.84 +/- 0.16 mm control; 2.89 +/- 0.16 mm relaxed) and femoral (OD: 3.56 +/- 0.32 control; 3.66 +/- 0.31 mm relaxed) veins (2-3%). This alteration in myogenic tone results in over 120% change in lumen capacity for the human saphenous vein, whereas for the dog saphenous and femoral veins, the change in lumen capacity is less than 10%. The vessels showed a constriction to norepinephrine as well as a reversible dilation to Ca(2+)-free perfusion. These results support the hypothesis that an active myogenic response may play an important role in the regulation of vascular capacity in the human saphenous vein, which is subject to substantial pressure variations due to changing orthostatic loads.
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The "white coat effect" has been investigated by non-invasive automatic blood pressure monitoring in patients with hypertension, defined by casual blood pressure readings. A significant "white coat effect" has been demonstrated in 30 (32%) of the 93 patients: the average values were 17/9 mmHg and 6 beat/min, the highest values were 37/29 mmHg and 13 beat/min. The examination has been repeated after 24 hours in 11 cases and the phenomenon was reproducible. The "white coat effect" did not disappear even when the changes were compared to the averages of three subsequent automatic blood pressure measurements. There were significantly more women, than men among the "white coat" positive patients. However, no difference was found in age, occupation and the known duration of hypertension. Neither was any correlation between the "white coat effect" and the blood pressure reaction to mental arithmetic test. It is emphasized that the casual readings can significantly overestimate the blood pressure. This finding must be considered especially in the diagnosis of borderline hypertension.
The present study was executed in order to get further data on the role of vessel wall constituents in prostanoid synthesis and on the effect of anorganic constituents on it. Prostacyclin and tromboxane production of rat aortic tissue slices with intact endothelium and after mechanical as well as chemical endothelium removal were studied. The effects of hypoxia and changes in the ionic milieu on the release of these prostanoids were also examined. The tissue slices were incubated in normal or in modified Krebs-Ringer solution, bubbled with 95% O2 and 5% CO2 (with the exception of the studies in hypoxic conditions). Prostacyclin and thromboxane release was determined by specific radioimmunoassay of the stable metabolites, 6-keto-PGF1 alpha and TxB2, from the incubation medium. 174 tissue samples obtained from 164 rats were studied. Mechanical removal of the endothelium increased prostacyclin production of the aortic segments about fivefolds from a basal rate of 52.9 +/- 19.4 ng/gr/min, while it had no significant effect on thromboxane release (basal rate 0.83 +/- 0.13 ng/gr/min). Treating the endothelium with 1.0 M HCl almost totally suppressed prostacyclin release. Lowering the partial oxygen tension of the incubation medium significantly decreased the production of prostacyclin, while release of TxB2 somewhat increased. Increasing the Ca2+ concentration of the medium between 0-5 mM the release of prostacyclin was augmented and the release of thromboxane was diminished. Potassium free medium caused a very large increase in prostacyclin release of the tissue slices. The results show that release of vasoactive prostanoids from isolated rat aortic wall is dependent not exclusively on the endothelium and that various methods of endothelium removal may have distinct influences on prostacyclin and thromboxane productions. The changes in anorganic constituents of the surrounding medium could massively affect prostacyclin and thromboxane production of rat aortic tissue. The alternative effects of the above listed treatments on the release of prostacyclin and thromboxane from the rat aortic wall suggest the existence of different mechanisms in the control of the production of the two major prostanoids possessing opposite physiological effects.
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A combined intraluminal nonenzymatic-enzymatic digestion procedure was carried out in situ on the common carotid arteries of 21 human cadavers with the aid of a four-way double balloon catheter. Denaturing pretreatment with NaOH, 2.5 mol for 20 min followed by crude pancreatic extract, 20 mg/ml for 20 min were used. Mechanical properties of cylindrical segments were measured in vitro, and compared with contralateral control segments. The inner radius increased and wall thickness decreased significantly at each pressure level in the 0-200 mmHg (0-26.7 kPa) intraluminal pressure range. Volume of wall material per unit length of the segment decreased by 11.6%, cross-section of the lumen at 100 mmHg (13.3 kPa) intraluminal pressure increased by 13.6%. These results show that the internal layers of human arteries can be removed by enzyme digestion increasing the lumen, while intact (medial and adventitial) layers still can give sufficient strength to the arterial wall.
The effects of gamma-aminobutyric acid (GABA) and some GABA ergic compounds were examined on the spontaneous contractile activity of the ampullar segment of human Fallopian tubes in vitro. In both circular and longitudinal smooth muscle layers, GABA increased the frequency, and decreased the amplitude of the contractions. In longitudinal muscle layer, this effect occurred independently of endocrine status, while in the circular muscle layer, the amplitude was affected only in follicular phase and in postmenopause, but not in the luteal phase. Baclofen mimicked the effects of GABA, whereas muscimol and bicuculline failed to influence the contractility. Our findings suggest that, in the ampulla of the human oviduct, GABAB-receptors may be involved in the regulation of motility, and thus in the modulation of ovum transport and fertility.
Authors studied changes of femoral vein developed by the effect of examinations experimental lymphoedema in dogs. Light and electronmicroscopic were performed from femoral vein of animals killed on 3rd and 14th postoperative day, and biomechanical examinations were done too from dogs killed on 14th postoperative day. In vessel wall edema, fibrosis, and in valves infiltration consisting of macrophages, neutrophilic granulocytes and of mesenchymal cells were observed. Biomechanical examinations did not show significant deviation. Their results suggest the possibility that extremital lymphoedema also in man may contribute to development of varicosity or to its aggravation. Experimental lymphoedema of lower limb of dog can be proposed as model experiment to the complex study of pathogenesis of development of varix.
In order to understand the participation of the geometrical and elastic properties of the large cerebral arteries in the maintenance of brain circulatory homeostasis, biomechanical properties of isolated internal carotid artery (extracranial part) and vertebral artery (intrathoracic part) were investigated both in a relaxed and in an activated (3x 10(-6) mol.l-1 norepinephrine) state of the smooth muscle. Quasi-static large deformation mechanical test was carried out by means of changing the intraluminal pressure slowly (2.5 mmHg.sec-1) and cyclicly in a range of 0-250 mmHg at in vivo length while external diameter was recorded continuously as a function of the intraluminal pressure. Maximum active tangential strain was found to be -2.7 +/- 1.6% at 70 mmHg for the internal carotid artery, and -5.9 +/- 1.1% at 100 mmHg for the vertebral artery. Incremental elastic modulus decreased and distensibility increased in both arteries following smooth muscle activation, these alterations, however, were larger in the case of the vertebral artery. A U-shaped characteristic impedance of vertebral artery was found both in relaxed and in constricted states of this vessel. Minimum values for the relaxed and the activated segments were found at 90 mmHg and 120 mmHg, respectively. These results support the hypothesis that certain biomechanical properties of the large arteries, like impedance, can be regarded as controlled variables that may contribute to the optimization of circulatory functions.
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In order to study the long-term effect of impaired lymphatic drainage on the mechanical properties of the arterial wall, cylindrical femoral artery segments from 10 mongrel dogs after 2 weeks of hindlimb lymphatic occlusion were subjected to in vitro mechanical test and compared with the contralateral, sham-operated segments. Smooth muscle contraction was induced by norepinephrine (7.4 X 10(-6) M) and smooth muscle relaxation by papaverine (1.6 X 10(-4) M). As a result of 2 weeks of lymphatic occlusion, wall thickness increased from 243 +/- 18 to 343 +/- 35 microns (P less than 0.02), inner radius decreased from 1.69 +/- 0.11 to 1.42 +/- 0.12 mm (P less than 0.01) and elastic modulus decreased from 1.23 X 10(6) to 0.55 X 10(6) N/m2 (P less than 0.01), when determined at 100 mm Hg (13.3 kPa) intraluminal pressure and with relaxed smooth muscle. The contractile apparatus was able to produce active strain in the vessels with lymphostasis and at physiological pressures not significantly different from the controls (0.89 +/- 0.02 vs. 0.91 +/- 0.02), but at significantly lower levels of tangential stress. Active stress decreased significantly. This study shows that a reorganization of the vessel wall mechanical force-bearing elements occurs in lymphostasis, which, in some respects, resembles the mechanical alterations found in different forms of atherosclerosis.
The magnitude and mechanism of myogenic response of vascular smooth muscle (SM) in rat distal saphenous vein was assessed from SM membrane potential (Em) measured in situ and in vitro with glass microelectrodes and from active and passive stress and strain calculated from changes in vessel diameter measured in vitro via videomicroscopy. Elevation of intraluminal pressure from 2.2 +/- 0.2 (SE) mmHg (control) to 15 +/- 0.8 mmHg for 1 h in a series of in vitro vessel segments perfused with physiological salt solution at 0.2 ml/min induced a maintained and reversible depolarization of 18 +/- 0.9 mV. A 7.6 +/- 0.4-mmHg pressure increase induced a 12.9 +/- 1.2-mV depolarization in a second series. In a third series, 5-mmHg pressure increments induced significant increments in active isometric stress and isobaric strain. Opening an acute, reversible in situ femoral artery to saphenous vein shunt caused a 4- to 5-mmHg venous pressure elevation, a 10-fold increase in venous blood flow, and a 12.1 +/- 0.9-mV venous SM depolarization. Thus a short-term pressure load causes sustained, reversible venous SM cell depolarization both in vitro and in situ, coupled with active strain and stress generation in the vein wall. These results support our hypothesis that SM of peripheral veins can contribute to an intrinsic capacity autoregulation.
Femoral vein pressure in adult male Sprague-Dawley rats kept in specially designed tubelike cages rose immediately from a control value of 2.9 +/- 0.2 (SE) mmHg to a gravity-induced sustained value of 5.9 +/- 0.2 mmHg on initiation of a 2-wk 45 degrees head-up tilt period. Femoral arterial pressure was not altered by tilting. In 2 wk mean external diameter, but not total wall thickness, of in vitro distal saphenous vein segments from tilted rats was increased approximately 30% above that of segments from nontilted controls at each of four successive 5-mmHg intralumenal pressure (IP) increments applied between 0 and 20 mmHg. Consequently, in tilted rats isobaric stress was increased 38% at low and 24% at high IP, whereas incremental distensibility was decreased at mid IP. Vascular smooth muscle (VSM) in tilted rat vein, but not artery, was hyperpolarized relative to controls both in vitro at normal physiological pressures [membrane potential (Em) = -58.2 +/- 0.8 vs. -52.4 +/- 0.8 mV, respectively] and in situ during local neural blockade (Em = -61.3 +/- 2.3 vs. -53.5 +/- 0.5 mV, respectively). The conclusion is that a moderate chronic elevation of IP in a vein results in hyperpolarization of its VSM and an elevation of its total capacity due to an as yet unexplained mechanism of physiological adaptation.
Lymphatic obstruction leads to leakage of protein into the vessel wall that is coupled with edema formation and smooth muscle degeneration. To clarify the mechanical effect of these changes, lymphatic trunks, draining the femoral artery, were stained with Evans blue and then ligated in dogs anesthetized with pentobarbital sodium (n = 11). Sham ligation was performed on these lymphatic trunks in the opposite hindlimb (n = 11). Three days later, 7- to 30-mm segments of both femoral arteries were studied in vitro. Intraluminal pressure was cycled between 5 and 250 mmHg at 5 mmHg/s, and external diameter was recorded in both relaxed and activated (norepinephrine, 3 x 10(-5) mol/l) state of smooth muscle. Mechanical parameters were computed for 10-mmHg pressure increments. After lymphatic obstruction, strain energy density and distensibility of the passive wall components as well as isobaric active tangential strain were decreased by a maximum of 27, 59, and 54%, respectively; active tangential stress and elastic modulus, as a function of tangential stretch, was decreased by a maximum of 62%, and increased by 61%, respectively. These results indicate that short-term intramural lymphostasis reduces smooth muscle reactivity and induces vascular stiffening.