Heterogeneity of membrane properties in vascular muscle cells from various vascular beds

It is becoming increasingly more apparent that vascular smooth muscle cannot be treated as a homogeneous group and cannot be compared to other types of smooth muscle at least in terms of responsiveness to vasoactive agents. This heterogeneity may have as part of its basis differences in the molecular structure at the level of the plasma membrane. Such differences manifest themselves in terms of resting membrane potential (Em), response to cardiac glycosides, ionic conductances, and membrane responses to neurotransmitters. Results show that the middle cerebral artery of the cat has a higher Em and depolarizes to excess K+ with a steeper slope than other peripheral arteries of the same animal. Furthermore, cerebral arteries from different areas of the brain exhibit distinctly different resting membrane properties as well as different responses to norepinephrine. In addition, cerebral arteries exhibit a high degree of electromechanical coupling not always observed in other peripheral arteries.     

Structure Identification of Uncertain Complex Networks Based on Anticipatory Projective Synchronization

This paper investigates a method to identify uncertain system parameters and unknown topological structure in general complex networks with or without time delay. A complex network, which has uncertain topology and unknown parameters, is designed as a drive network, and a known response complex network with an input controller is designed to identify the drive network. Under the proposed input controller, the drive network and the response network can achieve anticipatory projective synchronization when the system is steady. Lyapunov theorem and Barbǎlat’s lemma guarantee the stability of synchronization manifold between two networks. When the synchronization is achieved, the system parameters and topology in response network can be changed to equal with the parameters and topology in drive network. A numerical example is given to show the effectiveness of the proposed method.     

Vasoconstrictor responsiveness of hind body vascular beds is diminished in tail-suspended rats

It is well known that the mechanisms of occurrence of orthostatic intolerance induced by exposure to microgravity deal with multiple factors including alterations of arteries. In the previous works, the diminished contractile responsiveness of abdominal aorta and hind body medium-sized conduit arteries, mesenteric artery and femoral artery, were observed in tail-suspended rats, and the data showed that the femoral artery have subjected to the greatest changes. These results suggested that the vasoreactivity of resistance vessels might be affected by the real or simulated microgravity. Since the arterioles are the main site of peripheral resistance and of its regulation. Therefore, changes in responsiveness of arteriolar network, especially in the lower/hind body region, would be of primary importance in the genesis of postflight orthostatic intolerance. The aim of the present work was to examine whether simulated weightlessness may lead to an impairment in vasoconstrictor responsiveness in hind body vascular beds.     

Spontaneous Local Gamma Oscillation Selectively Enhances Neural Network Responsiveness

Synchronized oscillation is very commonly observed in many neuronal systems and might play an important role in the response properties of the system. We have studied how the spontaneous oscillatory activity affects the responsiveness of a neuronal network, using a neural network model of the visual cortex built from Hodgkin-Huxley type excitatory (E-) and inhibitory (I-) neurons. When the isotropic local E-I and I-E synaptic connections were sufficiently strong, the network commonly generated gamma frequency oscillatory firing patterns in response to random feed-forward (FF) input spikes. This spontaneous oscillatory network activity injects a periodic local current that could amplify a weak synaptic input and enhance the network's responsiveness. When E-E connections were added, we found that the strength of oscillation can be modulated by varying the FF input strength without any changes in single neuron properties or interneuron connectivity. The response modulation is proportional to the oscillation strength, which leads to self-regulation such that the cortical network selectively amplifies various FF inputs according to its strength, without requiring any adaptation mechanism. We show that this selective cortical amplification is controlled by E-E cell interactions. We also found that this response amplification is spatially localized, which suggests that the responsiveness modulation may also be spatially selective. This suggests a generalized mechanism by which neural oscillatory activity can enhance the selectivity of a neural network to FF inputs.     

Effect of vasoconstriction on longitudinal distribution of pulmonary vascular pressure and volume

We used an improved version of the low-viscosity bolus method to evaluate longitudinal (arterial-to-venous) differences in the sensitivity of the dog lung lobe vasculature to selected vasoconstrictor stimuli, including hypoxia, and serotonin, histamine, and norepinephrine infusions. This method revealed a bimodal distribution of local vascular resistance vs. cumulative vascular volume under the zone 3 conditions studied. Our interpretation of the two modes of relatively high resistance is that they correspond to high resistance per unit volume segments of the arteries and veins upstream and downstream from the relatively low resistance per unit volume capillary bed. Thus an increase in the height of the upstream and downstream modes of the resistance distribution suggests constriction in small arteries and veins, respectively. Horizontal displacement of the modes along the cumulative volume axis suggests changes in the distribution of volume among the arteries, veins, and capillary bed. By use of these criteria, the results are consistent with the concept that each of the vasoconstrictor stimuli studied had a different longitudinal response pattern. Hypoxia constricted mainly small arteries, whereas serotonin constricted small and large arteries. Histamine constricted large and small veins, and norepinephrine constricted large and small veins and arteries.     

Synthesis and vascular actions of an arachidonic acid ethylene-diamino-triethyl-ester (AA-EDTA) derivative

An ethylene-diamino-triethyl-ester derivative of arachidonic acid (AA-EDTA) was newly synthesized and tested for its coronary vasoactivity in isolated perfused cat coronary arteries. This arachidonic acid analog exerted a coronary vasodilator effect and significantly antagonized the coronary vasoconstrictor effect of LTD4. The constrictor response to the thromboxane analog carbocyclic thromboxane A2 was unaffected by AA-EDTA. These properties of AA-EDTA may be useful in counteracting the vasoconstrictor influence of leukotrienes in situations such as coronary artery vasospasm.     

Effect of cooling on vascular smooth muscle from the thirteen-lined ground squirrel

Peripheral vascular resistance in the ground squirrel (Spermophilus tridecemlineatus) increases when the animal enters hibernation. The goals of this study were to determine if a change in vascular reactivity contributes to this hemodynamic response, and to compare the effects of temperature on vascular responsiveness in a hibernator (ground squirrel) and a nonhibernating mammal (rat). Helically cut strips of aortae and femoral arteries were mounted in organ chambers (37 degrees C) and isometric contractions were recorded. The arteries were made to contract in response to exogenous norepinephrine (5.9 X 10(-7) M). Cooling the organ chamber (11 degrees C) potentiated contractions to norepinephrine (5-15% increase) in ground squirrel femoral arteries but depressed those (80-100% decrease) in ground squirrel aortae and rat aortae and femoral arteries. Contractions in response to depolarizing concentrations of potassium in ground squirrel femoral arteries were depressed by cooling (11 degrees C), suggesting that the augmented response to norepinephrine at low temperature is specific. Treatment with indomethacin, propanolol, and ouabain did not alter the potentiating effect of temperature on contractions to norepinephrine in ground squirrel femoral arteries. Apparently, the potentiation is not related to prostaglandins generated in the vascular wall, to blockade of beta-adrenergic receptors, nor to inhibition of the electrogenic sodium pump. The observations are consistent with the hypothesis that a change in vascular responsiveness contributes to the regional control of blood flow in hibernation. This adaptive response is specific in that it does not occur in the aorta of the ground squirrel and the response is not present in the vasculature of the rat, a nonhibernating mammal.     

Effect of simulated microgravity on vascular contractility

Microgravity was simulated inSprague-Dawley (SD) and Wistar (W) rats by using a tail harness toelevate the hindquarters, producing hindlimb unweighting (HU). After 20 days of HU treatment, blood vessels from both HU and control rats werecut into 3-mm rings and mounted in tissue baths for the measurement ofisometric contraction. HU treatment decreased the contractile responseto 68 mM K⁺ in abdominal aortafrom W rats. HU treatment also decreased the contraction to 68 mMK⁺ in carotid arteries from bothrat strains and in femoral arteries from W but not SD rats. HUtreatment reduced the maximal response to norepinephrine in allarteries except the femoral from SD rats. HU treatment reduced themaximal response of jugular vein from W rats to 68 mMK⁺ but had no effect on thatresponse in femoral vein from either rat strain. HU treatment also hadno significant effect on the maximal response to norepinephrine inveins. These results demonstrate that HU treatment caused a nearlyuniversal reduction of contractility in arteries, but generally had noeffect in veins.

     

Synthesis and vascular actions of an arachidonic acid ethylene-diamino-triethyl-ester (AA-EDTA) derivative

An ethylene-diamino-triethyl-ester derivative of arachidonic acid (AA-EDTA) was newly synthetized and tested for its coronary vasoactivity in isolated perfused cat coronary arteries. This arachidonic acid analog exerted a coronary vasodilator effect and significantly antagonized the coronary vasoconstrictor effect of LTD₄. The constrictor response to the thromboxane analog carbocyclic thromboxane A₂ was unaffected by AA-EDTA. These properties of AA-EDTA may be useful in counteracting the vasoconstrictor influence of leukotrienes in situations such as coronary artery vasospasm.     

A system model for investigating passive electrical properties of neurons.

Passive membrane properties of neurons, characterized by a linear voltage response to constant current stimulation, were investigated by busing a system model approach. This approach utilizes the derived expression for the input impedance of a network, which simulates the passive properties of neurons, to correlate measured intracellular recordings with the response of network models. In this study, the input impedances of different network configurations and of dentate granule neurons, were derived as a function of the network elements and were validated with computer simulations. The parameters of the system model, which are the values of the network elements, were estimated using an optimization strategy. The system model provides for better estimation of the network elements than the previously described signal model, due to its explicit nature. In contrast, the signal model is an implicit function of the network elements which requires intermediate steps to estimate some of the passive properties.     

Modeling of angioadaptation: insights for vascular development

Vascular beds are generated by vasculogenesis and sprouting angiogenesis, and these processes have strong stochastic components. As a result, vascular patterns exhibit significant heterogeneity with respect to the topological arrangement of the individual vessel segments and the characteristics (length, number of segments) of different arterio-venous pathways. This structural heterogeneity tends to cause heterogeneous distributions of flow and oxygen availability in tissue. However, these quantities must be maintained within tolerable ranges to allow normal tissue function. This is achieved largely through adjustment of vascular flow resistance by control of vessel diameters. While short-term diameter control by changes in vascular tone in arterioles and small arteries plays an important role, in the long term an even more important role is played by structural adaptation (angioadaptation), occurring in response to metabolic and hemodynamic signals. The effectiveness, stability and robustness of this angioadaptation depend sensitively on the nature and strength of the vascular responses involved and their interactions with the network structure. Mathematical models are helpful in understanding these complex interactions, and can be used to simulate the consequences of failures in sensing or signal transmission mechanisms. For the tumor microcirculation, this strategy of combining experimental observations with theoretical models, has led to the hypothesis that dysfunctional information transport via vascular connexins is a major cause of the observed vascular pathology and increased heterogeneity in oxygen distribution.     

Cytokines and vascular reactivity in resistance arteries

Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-alpha, IL-1beta, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and atherogenesis and reinforce the link between inflammation and vascular disease.     

A hierarchical neural network model for associative memory

A hierarchical neural network model with feedback interconnections, which has the function of associative memory and the ability to recognize patterns, is proposed. The model consists of a hierarchical multi-layered network to which efferent connections are added, so as to make positive feedback loops in pairs with afferent connections. The cell-layer at the initial stage of the network is the input layer which receives the stimulus input and at the same time works as an output layer for associative recall. The deepest layer is the output layer for pattern-recognition. Pattern-recognition is performed hierarchically by integrating information by converging afferent paths in the network. For the purpose of associative recall, the integrated information is again distributed to lower-order cells by diverging efferent paths. These two operations progress simultaneously in the network. If a fragment of a training pattern is presented to the network which has completed its self-organization, the entire pattern will gradually be recalled in the initial layer. If a stimulus consisting of a number of training patterns superposed is presented, one pattern gradually becomes predominant in the recalled output after competition between the patterns, and the others disappear. At about the same time when the recalled pattern reaches a steady state in he initial layer, in the deepest layer of the network, a response is elicited from the cell corresponding to the category of the finally-recalled pattern. Once a steady state has been reached, the response of the network is automatically extinguished by inhibitory signals from a steadiness-detecting cell. If the same stimulus is still presented after inhibition, a response for another pattern, formerly suppressed, will now appear, because the cells of the network have adaptation characteristics which makes the same response unlikely to recur. Since inhibition occurs repeatedly, the superposed input patterns are recalled one by one in turn.     

High and low dietary potassium effects on rat vascular sodium pump activity

Studies of renal and other tissues suggest that chronic elevation or reduction of dietary potassium intake could affect vascular smooth muscle sodium pump (Na-pump) activity. To examine this possibility, the effects of 3 weeks of low (LK: 4 mmole KCl/kg chow), normal (NK; 162 mmole/kg), and high (HK; 1350 mmole/kg) dietary potassium intake on Na-pump activity, the Na-pump activity response to changes in extracellular potassium concentration, and Na-pump site density were determined in tail arteries of rats. Plasma potassium concentration was elevated by 21% in HK rats and reduced by 45% in LK rats. When incubated in autologous plasma, compared to arteries from NK rats, Na-pump activity was decreased in the tail arteries from LK rats but not altered in those from HK rats. When arteries from NK and LK rats were incubated in autologous plasma with the potassium concentration increased to equal that of the HK rats, Na-pump activity exceeded that of HK rat arteries: Na-pump activity of arteries incubated in autologous plasma did not differ from that of arteries incubated in Krebs-Henseleit buffer with the potassium concentration adjusted to equal that of the plasma. Tail artery Na-pump activity for all three dietary potassium groups increased as potassium concentration of the incubation medium was increased from 1 to 12 mM; Na-pump activity was similar for the NK and LK rats at all potassium concentrations, but Na-pump activity of HK rat arteries was less than that of NK arteries at high extracellular potassium concentrations. Na-pump site density was not altered by either HK or LK diet. It is concluded that in tail arteries of rats fed the LK diet, chronically decreased extracellular potassium results in chronically decreased Na-pump activity. In contrast, an adaptive change occurs in tail arteries of rats fed HK diet, such that Na-pump activity remains at normal levels despite elevated extracellular potassium; this adaptive response to chronically increased dietary potassium does not appear to be the result of decreased Na-pump site density.     

Development of fetal vascular responses to endothelin-1 and acetylcholine in the sheep

Responses to K(+), endothelin-1 (ET-1), and acetylcholine (ACh) of isolated adrenal, femoral, middle cerebral, and renal arteries from fetal [110--145 days gestational age (dGA, term approximately 148 dGA)] and 0- to 24-h newborn (NB) lambs were evaluated using the technique of wire myography. Responses at distinct developmental ages for each vascular bed were compared. In all arteries sensitivity to K(+)-induced vasoconstriction was similar at all fetal age points examined. In contrast, sensitivity to ET-1 increased with increasing fetal age in arteries from all vascular beds. The magnitude of the maximal vasoconstriction was positively correlated with GA for K(+) in adrenal, femoral, and cerebral arteries and for ET-1 in femoral, cerebral, and renal arteries. Cerebral arteries showed a greater sensitivity when compared with the other systemic arteries to K(+) and ET-1 at all fetal ages and to K(+) in NB. ACh evoked relaxatory responses in fetal and NB femoral and adrenal arteries. However, renal arteries relaxed comparatively less in response to ACh, and no vasodilation was noted in middle cerebral arteries at any age points examined. For femoral arteries ACh-induced vasorelaxation decreased with increasing GA but was restored in arteries from NB lambs. In summary, the responsiveness of isolated resistance arteries varies with developmental age in the fetal and perinatal sheep and these effects are both agonist and vascular bed specific. The augmented sensitivity in response to ET-1 of middle cerebral compared with other systemic arteries may reflect the importance of cerebral blood flow control during this critical developmental period.     

Effect of periodic alterations in shear on vascular macromolecular uptake

Experiments were carried out in swine to test the hypothesis that changes in the fluid dynamic environment of the arterial wall, with time constants of several minutes to perhaps a few hours, prompt adaptive responses that transiently increase endothelial permeability. After parenteral Evans Blue Dye (EBD) administration, the hemodynamics of the external iliac arteries of the experimental animals were altered using a reversible arteriovenous femoral shunt. For 3 h, the shunt was opened and closed with a period (tau) between 1-180 min. Subsequently, the animal was euthanized and the iliac vessels were photographed en face to obtain the distribution of EBD-bound albumin uptake by the tissue during its exposure to the dye. Albumin uptake increases with tau in a fashion that can be explained by an a priori model of the adaptive permeability response, with a time constant of about an hour.     

Chloride channel activity of vascular smooth muscle in the spontaneous hypertensive rats

To characterize the activity of the Ca2+-activated Cl- channels in vascular smooth muscle (VSM) of the spontaneous hypertensive rats (SHR), the isolated mesenteric vascular beds and tail artery strips were preparated from SHR and Wistar rats aged 7-8 weeks. The changes in contractile response to norepinphrine (NE) were taken as an index of vascular mortion. Results showed that the contractile responses of mesenteric arteries and tail arteries to NE in SHR were significantly greater than that in Wistar rats. The inhibition magnitude of the contractile response by Ca2+-activated Cl- channel blocker, niflumic acid in SHR was significantly less than that in Wistar rats. Decreasing the extracellular Cl- concentration increased the contractile response to NE significantly, but the amplitude of enhanced contractile response in SHR was greater than that in Wistar rats. It can be concluded that NE-induced contraction was enhanced in SHR, which is partly due to an increase in Cl- efflux through the Ca2+-activated Cl- channels. The chloride channel activity may be increased in association with the elevation of blood pressure.     

Chronic hypoxia alters prejunctional alpha(2)-receptor function in vascular adrenergic nerves of adult and fetal sheep

The impact of development and chronic high-altitude hypoxia on the function of prejunctional alpha(2)-adrenoceptors was studied by measuring norepinephrine release in vitro from fetal and adult sheep middle cerebral and facial arteries. Blockade of prejunctional alpha(2)-adrenoceptors with idazoxan significantly increased stimulation-evoked norepinephrine release in normoxic arteries. This effect was eliminated after chronic hypoxia in cerebral arteries, with a tendency to decline in fetal facial arteries. After chronic hypoxia, the capacity to release norepinephrine declined in fetal middle cerebral arteries with a similar trend in facial arteries. Norepinephrine release was maintained in adult arteries. During development, stimulation-evoked norepinephrine release from middle cerebral and facial arteries was higher compared with adult arteries. In fetal arteries, adrenergic nerve function declined after chronic hypoxia. However, in adult arteries, adrenergic nerves adapted to chronic hypoxia by maintaining overall function. This differential adaptation of adrenergic nerves in fetal arteries may reflect differences in fetal distribution of blood flow in response to chronic hypoxic stress.     

Modulation of cerebral vascular tone by activated glia: involvement of nitric oxide

The ability of activated glia to affect cerebral vascular tone has been evaluated using an in vitro experimental system in which basilar arteries were incubated with glial cultures activated by treatment with lipopolysaccharide (LPS). Vascular tone was measured with an isometric myograph. Contraction in response to high KCl and serotonin was reduced in arteries co-incubated for 24 h with LPS-activated glia, whereas the response to acetylcholine was not modified. The reduced contraction was prevented when the nitric oxide synthase (NOS) inhibitor L-N-nitro-arginine (L-NNA) was added throughout the whole incubation time (activation of glial cells with LPS + co-incubation of glial cells with cerebral arteries). Under these conditions, nitrite levels were drastically reduced. A reduced contraction to KCl was also observed after treatment of the cerebral vessel with sodium nitroprusside. In contrast, L-NNA added to the vessel did not modify the response to contracting stimuli and the expression of endothelial NOS was not modified in cerebral arteries pre-incubated with activated glia. These results suggest that activated glia, which finds an in vivo correlate in several neuropathological conditions, can contribute to changes of vascular tone by modifying the levels of nitric oxide (NO) to which the vessel is exposed.     

The inhibitory actions of acebutolol and propranolol on the contractile response to 5-hydroxytryptamine in various isolated vascular smooth muscles

Pretreatment with acebutolol or propranolol at high concentrations had an inhibitory effect on the contractile response to 5-hydroxytryptamine (5-HT) in most vascular smooth muscles such as rabbit aorta and basilar, mesenteric, renal, femoral arteries and cat coronary artery. The inhibitory actions of both agents were generally greater than on the responses to excess Ca2+ and potassium. In rabbit renal arteries, acebutolol had no effect on the response to 5-HT but inhibited the responses to excess Ca2+ and potassium. Propranolol had a marked inhibitory effect on the response to 5-HT. In all preparations used, the contractions induced by norepinephrine (NE) and histamine showed a much greater resistance to the effect of acebutolol and propranolol than the contractions induced by 5-HT, Ca2+ and potassium. Nifedipine had no inhibitory effect on the response to 5-HT in most of the preparations. Nifedipine inhibited the response to 5-HT only in the basilar arteries. The inhibitory actions of propranolol on the response to 5-HT was greater than that of acebutolol. The inhibitory action of acebutolol and propranolol on the response to 5-HT may be related to mechanisms other than the beta-adrenoceptor blocking action of the drugs. The possible mechanisms of inhibitory action of both beta-adrenoceptor antagonists on 5-HT are discussed.