Effect of emotional stress on the contractility, adrenoreactivity and calcium sensitivity of smooth muscles of the portal vein in spontaneously hypertensive rats

The emotional stress decreased contractility and adrenoreactivity in normotensive rats, while in spontaneously hypertensive rats (SHR) the changes were less pronounced. The changes in adrenoreactivity, as well as increased permeability of smooth muscle cells for calcium and reduced reactivity to exogenous calcium revealed in hypertensive animals contribute to high resistance of portal vein smooth muscles to stress.     

Mechanism of the effect of dibasol on the contractile and electric activities of the smooth muscle of the portal vein

The effects of dibasol on spontaneous electrical and contractile activities as well as on the reactions evoked by hyperkalemic solution and noradrenaline were studied in smooth muscle of rabbit portal vein. It was shown that dibasol blocked the potential-operated influx Ca2+ into smooth muscle cells. The noninactivating calcium channels were found to be more sensitive to dibasol than inactivating ones. Significant part of the tonic contraction induced by noradrenaline was resistant to dibasol suggesting its weak effect on Ca2+ influx through calcium channels operated by alpha 1-adrenoceptors. It is supposed that vasodilative effect of dibasol is associated with blocking the influx Ca2+ through potential-operated noninactivating calcium channels into smooth muscle cells.     

Comparative evaluation of the protective effect of adaptation to short-term stress exposures in damage to the heart and portal vein from long-term stress

The effect of the preliminary adaptation to short-term stress actions carried out under different conditions was studied in the myocardium and vascular smooth muscle damaged by long-term immobilization stress. The preliminary adaptation performed under "sparing" conditions was shown to protect more effectively the right atrial myocardium and portal vein against damages induced by long-term immobilization than that carried out under stringent conditions. The sparing adaptation allowed avoiding the appearance of the structural "price" of the adaptation, i.e. the depression of myocardial contractile function induced by adaptation itself.     

Smooth muscle function of the portal vein in spontaneously hypertensive rats

Increased contractility and adrenoreactivity of the portal vein smooth muscles were revealed in spontaneously hypertensive rats (SHR) only at the early stage of the disease. In stable hypertension the changes were milder both at the early and chronic stages. Portal vein smooth muscles were capable of contracting in low-calcium medium, which suggests a membrane defect in the smooth muscles of animals with arterial hypertension.     

Effect of myocardial infarct on the cholinoreactivity of the heart atria and on their acetylcholine content

The effect of left ventricular experimental infarction (caused by left coronary artery ligation) on the isolated right atrium contractile function and acetylcholine content in both atria was studied in male Wistar rats. It was shown that a 24-hour infarction induced an increase in atrial chronotropic response to acetylcholine, which proved an increase in the pacemaker cholinoreactivity. Atrial inotropic response to acetylcholine characterizing the contractile myocardium cholinoreactivity remained unchanged. At the same time atrial endogenous acetylcholine content decreased fourfold. An increase in pacemaker cholinoreactivity was not accompanied by changes in its adrenoreactivity; those changes increased the pacemaker sensitivity to cholinergic influences which could help elucidate the ectopic excitation foci, thus promoting the onset of arrhythmia.     

Historical perspective on airway smooth muscle: the saga of a frustrated cell.

Despite the lack of a clearly defined physiological function, airway smooth muscle receives substantial attention because of its involvement in the pathogenesis of asthma. Recent investigations have turned to the ways in which the muscle is influenced by its dynamic microenvironment. Ordinarily, airway smooth muscle presents little problem, even when maximally activated, because unending mechanical perturbations provided by spontaneous tidal breathing put airway smooth muscle in a perpetual state of "limbo," keeping its contractile machinery off balance and unable to achieve its force-generating potential. The dynamic microenvironment affects airway smooth muscle in at least two ways: by acute changes associated with disruption of myosin binding and by chronic changes associated with plastic restructuring of contractile and cytoskeletal filament organization. Plastic restructuring can occur when dynamic length changes occur between sequential contractile events or within a single contractile event. Impairment of these normal responses of airway smooth muscle to its dynamic environment may be implicated in airway hyperresponsiveness in asthma.     

The effect of repeated acute mental stress on habituation and recovery responses in hemoconcentration and blood cells in healthy men

Acute mental stress elicits hemoconcentration and polycytosis. We investigated whether haematological response to repeated acute mental stress would habituate and be sustained 45 min and 105 min after stress. Twenty-four men underwent a 13-min stressor three times, one week apart; hematological variables were measured at week one and three. Hematocrit, hemoglobin, leukocytes, lymphocytes, erythrocytes, and thrombocytes all increased from rest to immediately post-stress (p's<.001). After 105 min of recovery, leukocytes and platelets both were higher, and hematocrit, hemoglobin, lymphocytes, and erythrocytes were all lower than at rest (p's<.001 to <.05). At all time points, hematocrit (p=.005) and erythrocytes (p=.006) were lower at week three than at week one. In contrast to an attenuation in systolic blood pressure increase from rest to immediately post-stress (p<.001), and in cortisol recovery from immediately post-stress to 45 min post-stress (p<.001), the magnitude of change in hemoconcentration and cell counts in stress and recovery experienced no habituation. Adjustment for stress-induced plasma volume shift altered findings: Elevated leukocytes post-stress persisted at 105 min (p<.001); any changes in lymphocytes became insignificant; erythrocytes decreased from rest to post-stress (p<.001) to increase again during recovery (p's<.05); platelets increased linearly between rest and 105 min of recovery (p=.005). We conclude that the magnitude of changes in hemoconcentration and blood cells during acute mental stress and recovery failed to habituate to stress repeats and, in part, sustained up to 105 min. Plasma volume shift accompanying stress affects the time course of stress polycytosis.     

F-actin capping (CapZ) and other contractile saphenous vein smooth muscle proteins are altered by hemodynamic stress: a proteonomic approach

Increased force generation and smooth muscle remodeling follow the implantation of saphenous vein as an arterial bypass graft. Previously, we characterized and mapped 129 proteins in human saphenous vein medial smooth muscle using two-dimensional (2-D) PAGE and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Here, we focus on actin filament remodeling in response to simulated arterial flow. Human saphenous vein was exposed to simulated venous or arterial flow for 90 min in vitro, and the contractile medial smooth muscle was dissected out and subjected to 2-D gel electrophoresis using a non-linear immobilized pH 3-10 gradient in the first dimension. Proteins were analyzed quantitatively using PDQuest 2-D software. The actin polymerization inhibitor cytochalasin B (1 microm) prevented increases in force generation after 90 min of simulated arterial flow. At this time point, there were several consistent changes in actin filament-associated protein expression (seven paired vein samples). The heat shock protein HSP27, identified as a three-spot charge train, showed a 1.6-fold increase in abundance (p = 0.01), but with reduced representation of the phosphorylated Ser(82) and Ser(15)Ser(82) isoforms (p = 0.018). The abundance of actin-capping protein alpha2 subunit CapZ had decreased 3-fold, p = 0.04. A 19-kDa proteolytic fragment of actin increased 2-fold, p = 0.04. For the four-spot charge train of gelsolin, there was reduced representation of the more acidic isoforms, p = 0.022. The abundance of other proteins associated with actin filaments, including cofilin and destrin, remained unchanged after arterial flow. Actin filament remodeling with differential expression and/or post-translational modification of proteins involved in capping the barbed end of actin filaments, HSP27 and CapZ, is an early response of contractile saphenous vein smooth muscle cells to hemodynamic stress. The observed changes would favor the generation of contractile stress fibers.     

Effect of emotional-pain stress on the adrenocholinoreactivity of the smooth muscle of the portal vein

Effect of emotional painful stress (EPS) on adreno- and cholinoreactivity of the portal vein was studied. EPS produced a significant decrease in adrenoceptor sensitivity of the vein to noradrenaline, which was not accompanied by a significant change of cholinoceptor sensitivity to acetylcholine. A possible mechanism of the phenomenon is discussed.     

Contractile responses to prostacyclin (PGI2) of isolated human saphenous and rat venous tissue.

Prostacyclin (PGI2), in a wide concentration range, produced neither contraction nor relaxation of isolated human saphenous vein. Isolated portal veins and vena cava from normal and spontaneously hypertensive rats (SHR) responded only with an increase in contractile tension when exposed to PGI2. This constrictor effect was absent in a calcium-free buffer. PGI2 failed to relax KCI contracted vena cava. The constrictor effect of PGI2 on portal vein was attenuated in a glucose-free, oxygen deficient buffer. No tachyphylaxis or tolerance to the constrictor effect of PGI2 was noted. Results emphasize that PGI2 may produce differing effects on vascular smooth muscle tension depending on species and type of blood vessel studied.     

Effect of atriopeptin on the adrenergic mechanism regulating blood vessel tonus

The direct action of atriopeptin on the cell regulation mechanism of the smooth muscle in isolated segments of the portal vein, aorta, pancreatic and cerebral arteries have been studied. It was found that atriopeptin induce the direct relaxation of the smooth muscle in the main vessels only (aorta, portal vein). In the cerebral and pancreatic arteries atriopeptin stops norepinephrine-induced contractions. The data obtained show that the action of the atriopeptin is mediated by Na+-K+ pump activation of smooth muscle cells and restricts vasoconstriction of catecholamine effect.     

Removal of the endothelium eliminates the stress-induced adrenoreactivity of the aorta

Emotional painful stress, experimental myocardial infarction and surgical stress induced by thoracotomy decreased the adrenoreactivity of isolated rat aorta with intact endothelium. The endothelium removal enhanced the response of aorta to noradrenaline, the enhancement being much more pronounced after stress exposures than in control. As a result, the adrenoreactivity of denuded preparations from stress-exposed animals appeared to be not reduced but, on the contrary, increased in comparison with the control. Since stress is known to increase the density and the affinity of alpha 2-adrenoceptors to a much more extent than those of alpha 1-adrenoceptors, it was suggested that the revealed in this work stress-induced potentiation of the inhibitory effect of the endothelium is due to the hyperactivation of endothelial alpha 2-adrenoceptors which mediate the release of endothelium derived relaxing factor. The significance of the effect in the development of pathological states of the organism is discussed.     

Effect of human plasma proteins on spontaneous contractile activity of rat mesenteric portal vein.

This study examines the effect of various plasma proteins from man on the spontaneous contractile activity of the rat portal vein. Albumin, gamma-globulin, alpha-globulin, beta-globulin (the major plasma proteins), and immunoglobulin IgG (the major immunoglobulin present in the gamma-globulin fraction) were obtained commercially. Mesenteric portal vein strips were prepared from rats and placed in a physiological salt solution in muscle baths for the measurement of longitudinal mechanical response. Portal veins exposed to albumin or gamma-globulin showed a dose-dependent increase in the spontaneous activity, whereas those exposed to alpha-globulin or alpha- and beta-globulin together showed a dose-dependent inhibition of spontaneous activity. Immunoglobulin IgG produced a dose-dependent increase in the spontaneous activity similar to that of gamma-globulin. The increased spontaneous activity produced by albumin was not prevented by ouabain but was inhibited by phentolamine. Spontaneous contractile activity was stimulated by albumin in the chemically (6-hydroxydopamine) denervated portal vein. These findings indicate that albumin acts in a manner similar to noradrenaline. The increased spontaneous activity caused by gamma-globulin (IgG) was inhibited by ouabain or verapamil. The effect of IgG was not dependent on alpha-adrenergic, cholinergic, histaminergic, serotoninergic, or renin angiotensin systems nor was it affected by removal of the endothelium. These observations may have implications in the pathophysiology of essential hypertension.     

Inhibitory effect of manganese on contraction of isolated rat aorta

The effects of MnCl2 on vascular smooth muscle contraction induced by noradrenaline (NA) and KCl were investigated. Rings segments from rat aorta were isolated and changes in isometric tension recorded. MnCl2 (10 microM and 1 mM) significantly attenuated the contractile responses to NA and KCI. There were also reductions in the contractile responses to CaCl2 in NA- and KCl-stimulated rings, after pretreatment with MnCl2. The magnitude of the phasic contraction to NA was significantly reduced in presence of MnCl2. The results suggest that MnCl2 inhibits vascular smooth muscle contraction by influencing a Ca2+-mediated mechanism.     

Rhythmic contractility in the hepatic portal “corkscrew” vein of the rat snake

Terrestrial, but not aquatic, species of snakes have hepatic portal veins with a corkscrew morphology immediately posterior of the liver. Relatively large volumes of venous blood are associated with this region, and the corkscrew vein has been proposed to function as a bidirectional valve that impedes gravitational shifts of intravascular volume. To better understand the functional significance of the corkscrew anatomy, we investigated the histology and contractile mechanisms in isolated corkscrew segments of the hepatic portal vein of a yellow rat snake (Pantherophis obsoletus). Morphologically, the corkscrew portal vein is here shown to have two distinct layers of smooth muscle – an inner circular layer, and an outer longitudinal layer, separated by a layer of collagen, – whereas only a single circular layer of smooth muscle is present in the adjacent posterior caval vein. Low frequency (~ 0.3 cycles*min^? 1) spontaneous and catecholamine-induced rhythms were observed in 11% and 89% of portal vein segments, respectively, but neither spontaneous nor agonist-induced cycling was observed in adjacent posterior (non-corkscrew) caval veins. Catecholamines, angiotensin II, or stretch increased the amplitude and/or frequency of contractile cycles. Ouabain, verapamil or indomethacin, but not tetrodotoxin, α-, or ß-adrenergic receptor antagonists, inhibited cyclical contractions indicating a dependence of these cycles on Na⁺/K⁺ ATPase, extracellular Ca²⁺ and prostanoid(s). These data suggest that the rhythmic contractility of the corkscrew segment of the ophidian portal vein may act in conjunction with its morphological features to improve venous return and to prevent retrograde shifts of blood that might otherwise pool in posterior veins.     

Cytoskeletal features in longitudinal and circular smooth muscles during development of the rat portal vein

Immunohistochemistry of -smooth muscle actin and desmin, two markers of smooth muscle cell differentiation, and electron-microscopic observation of thick filaments of myosin were performed on the media of the developing rat hepatic portal vein to gain insights into the chronology of differentiation of its longitudinal and circular smooth muscles. In accordance with the ultrastructural distribution of thin filaments, staining of -smooth muscle actin is lightly positive in the myoblasts at postnatal day 1 and then extends in probably all muscle cells of the developing vessel. Desmin, which appears later than -smooth muscle actin in the two muscles, is distributed throughout the longitudinal layer at day 8, whereas the first arrangements of thick filaments are detectable in most longitudinal muscle cells; at this stage, desmin and thick filaments are absent from the poorly differentiated circular muscle cells. The longitudinal muscle cells differentiate in a strikingly synchronized way from day 8 onwards, conferring a homogeneous structure to the developing and mature longitudinal layer. Several desmin-positive cells and a heterogeneous distribution of thick filaments occur in the circular muscle at day 14; the subsequent extension of these filaments in this layer results in a persisting heterogeneous distribution in the young 7-week-old adult. Many features of the mature smooth muscle cells are established within the third week in the longitudinal muscle, approximately one week before those of the circular layer. These results are consistent with the function of the longitudinal muscle as a spontaneously contractile smooth muscle unit, and emphasize the need for its fast maturation to fulfil its major role in the control of portal blood flow.     

Mechanisms of inhibition of the contractile activity in the ileo-caecal zone in rabbits under psychogenic stress

In experiments on unanaesthetized rabbits, myoelectric activity (contractile activity index) of distal ileum, caecum, and proximal colon in two sites was studied under stress induced by fastening a rabbit to the table in supine position. The stress caused sharp decrease (up to complete disappearance) of the contractile activity in all studied compartments of the ileocaecal intestine with partial or complete restoration after release of the animal. Nonselective blockade of pre- and postsynaptic alpha-adrenoceptor with dihydroergotoxin abolished the initial component of the specified inhibitory response. The latter was caused by "adrenergic inhibition" as a result of action of catecholamines circulating in blood on inhibitory smooth muscle alpha-adrenoceptor. Against the background of muscarinic cholinoceptor blockade, the stressor inhibition of ileocaecal contractile activity observed in control experiments was completely preserved. The periods of supression of ileoceacal contractile activity under stress resistant to blockade of alpha-, beta-adrenoceptor and muscarinic cholinoceptor, are caused by the mechanism of "nonadrenergic noncholinergic inhibition", which is realized at the expence of activation of the enteric inhibitory neurones.     

Heterogeneity of smooth muscle-associated proteins in mammalian brain microvasculature

In the brain, the microvascular system is composed of endothelial cells surrounded by a layer of pericytes. The lack of smooth muscle cells in this tissue suggests that any contractile function must be performed by one or both of these cell types. The present study was undertaken in order to identify cells in terminal blood vessels that contain smooth muscle-like contractile machinery. Endothelial cells were reactive with antibodies against smooth muscle myosin but showed no other smooth muscle-related features. In contrast, pericytes of intact microvessels showed a pattern of protein expression similar to that of smooth muscle cells. Pericytes also behaved in tissue culture like cultured smooth muscle cells, with regard to the changes in expression of smooth muscle-related proteins. These data confirm the close relationship between smooth muscle cells and pericytes, and point to their contractile function in the brain microvessels.     

Influence of dispersion in myosin filament orientation and anisotropic filament contractions in smooth muscle

A new constitutive model for the biomechanical behaviour of smooth muscle tissue is proposed. The active muscle contraction is accomplished by the relative sliding between actin and myosin filaments, comprising contractile units in the smooth muscle cells. The orientation of the myosin filaments, and thereby the contractile units, are taken to exhibit a statistical dispersion around a preferred direction. The number of activated cross-bridges between the actin and myosin filaments governs the contractile force generated by the muscle and also the contraction speed. A strain-energy function is used to describe the mechanical behaviour of the smooth muscle tissue. Besides the active contractile apparatus, the mechanical model also incorporates a passive elastic part. The constitutive model was compared to histological and isometric tensile test results for smooth muscle tissue from swine carotid artery. In order to be able to predict the active stress at different muscle lengths, a filament dispersion significantly larger than the one observed experimentally was required. Furthermore, a comparison of the predicted active stress for a case of uniaxially oriented myosin filaments and a case of filaments with a dispersion based on the experimental histological data shows that the difference in generated stress is noticeable but limited. Thus, the results suggest that myosin filament dispersion alone cannot explain the increase in active muscle stress with increasing muscle stretch.     

Time course of isotonic shortening and the underlying contraction mechanism in airway smooth muscle

Although the structure of the contractile unit in smooth muscle is poorly understood, some of the mechanical properties of the muscle suggest that a sliding-filament mechanism, similar to that in striated muscle, is also operative in smooth muscle. To test the applicability of this mechanism to smooth muscle function, we have constructed a mathematical model based on a hypothetical structure of the smooth muscle contractile unit: a side-polar myosin filament sandwiched by actin filaments, each attached to the equivalent of a Z disk. Model prediction of isotonic shortening as a function of time was compared with data from experiments using ovine tracheal smooth muscle. After equilibration and establishment of in situ length, the muscle was stimulated with ACh (100 μM) until force reached a plateau. The muscle was then allowed to shorten isotonically against various loads. From the experimental records, length-force and force-velocity relationships were obtained. Integration of the hyperbolic force-velocity relationship and the linear length-force relationship yielded an exponential function that approximated the time course of isotonic shortening generated by the modeled sliding-filament mechanism. However, to obtain an accurate fit, it was necessary to incorporate a viscoelastic element in series with the sliding-filament mechanism. The results suggest that a large portion of the shortening is due to filament sliding associated with muscle activation and that a small portion is due to continued deformation associated with an element that shows viscoelastic or power-law creep after a step change in force.