Mechanics of vascular smooth muscle contraction.
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Biomedical subjects
Publications and source records attributed to B Johansson.
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Acute hypertension, experimentally induced by intravenous injection of metaraminol in adult rabbits, rapidly induced a damage of the blood-brain barrier in the cerebral cortex, as visualized by Evans-blue-conjugated albumin and horseradish peroxidase. Extravasation of these two exogenous tracers was demonstrated to occur in arterioles, in capillaries and, rarely, in venules. Peroxidase passed the endothelial cell into the nervous tissue in either or three different ways, i.e. through channels, often sigmoidshaped, in the cytoplasm, and transendothelial pinocytosis. The third pathway could, although rarely, be demonstrated between adjacent endothelial cells after cleavage of junctional complexes. The tracer peroxidase was further spread along the blood vessel within the basement membrane and in the extracellular space of the brain. Damaged endothelial cells with diffuse cytoplasmic peroxidase activity and large vesicles were occasionally observed within the areas with blood-brain barrier injury. There were also signs of increased pinocytotic activity in endothelial cells outside the barrier damaged cortical areas. Nerve cells and neuroglial cells could show either a diffuse cytoplasmic peroxidase activity or a vesicular location of the tracer, or sometimes both. The observations are discussed in relation to previous studies on the mechanism of transendothelial passage of protein tracers at blood-brain barrier damage.
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Acute hypertension was induced by metaraminol at different time intervals following irradiation in rabbits exposed to unilateral X-ray irradiation against the brain (3000 R) and in control animals. Hypertension resulted in a few areas of Evans blue extravasation in control animals. In the irradiated animals there was a marked increase in tracer extravasation on the half of the brain exposed to X-rays, indicating an increased vulnerability of cerebral vessels to blood pressure increase after irradiation.
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Blood lymphocytes from the majority of 33 unselected and untreated patients with Hodgkin's disease were deficient in T-lymphocytes and their DNA synthesis induced by concanvallin A mitogen and PPD antigen was impaired. The spontaneous DNA synthesis during the first 24 hours of culture was often raised. The prognostic role of the lymphocyte deficiency was evaluated in a follow-up 10-22 months after institution of therapy. The lymphocyte functions were more commonly abnormal in patients responding poorly to treatment (incomplete remission, relapse after treatment, or death) than in patients entering complete remission. The lymphocyte deficiency seems to give information about prognosis in Hodgkin's disease in addition to histopathology, clinical stage, B-symptoms and age.
In a prospective study, sixty-five histologically verified Swedish cases of Hodgkin's disease were HL-A typed. The antigen frequencies in the patient group did not deviate from a group of normal controls. The frequency of HL-A8 was slightly increased in patients over 40 years (P less than 0.05). HL-A12 was markedly increased in patients below 40 years with a favourable histopathology (P less than 0.001). No association between sex or clinical stage and distribution of HL-A phenotypes was observed. The number of T-lymphocytes in blood and the spontaneous DNA synthesis and DNA synthesis induced by concanavalin A, pokeweed mitogen, phytohemagglutinin and PPD antigen in blood lymphocytes in vitro were determined in 60 patients. A significant increase of HL-A28 was noted in patients with advanced disease (P less than 0.01) and in patients responding poorly to PPD (P less than 0.001) and PWM (P less than 0.01). No correlation between HL-A antigen distribution and T-lymphocyte counts was observed.
5HIAA and HVA were determined in successive samples of CSF withdrawn at the lumbar and cisternal levels in connection with gas myelographic examinations in 16 patients. The mean of 5-HIAA in the first cisternal samples were 83 ng/ml (n equal to 8) and of HVA 143 NG/ML (N equal to 7). A sharp increase in the concentration of both metabolites, but particulary of HVA, was seen in successive lumbar samples. The ratio of cisternal/lumbar 5-HIAA was 3/1, and of HVA 10/1 in one patient in whom lumbar and cisternal CSF were obtained with 2 weeks' interval. The concentrations of monoamine metabolites in CSF obtained at lumbar puncture are thus highly dependent on the amount of fluid withdrawn. This fact should be taken into consideration when different materials are compared.
Unilateral X-ray exposure of brain increases the vulnerability of cerebral vessels to acute hypertension in the brain hemisphere exposed to radiation. A preventive effect of dexamethasone was observed when treatment with the drug was started before irradiation; but also when the drug was given 24 h before acute hypertension was induced, 1 week after irradiation.
The force-velocity relation of the rat portal vein has been studied during regular spontaneous contractions induced by elevated levels of [K-+]O AND [Ca-2+]o. No satisfactory description of the force-velocity relation was obtained by measuring shortening velocity in afterloaded isotonic contractions. Therefore the method of isotonic quick release was used, as this permits mechanical studies at specified instants of the contraction-relaxation cycle. The temporal development of the force-velocity relation in the phasic response was investigated. During a time interval in the rising phase of the contraction, at about the time for maximal dP/dt, the force-velicity curves were practically identical, suggesting a plateau in the intensity of active state. At later stages of the twitch the curves were progressively displaced towards the origin, the intercepts on both the force and the velocity axis becoming smaller. At the time of the isometric peak the maximal shortening velocity had declined relatively more than the isometric force. This is presumably caused by inhomogeneous activation of the muscle at the beginning of relaxation, The maximal force-velocity relation in the rising phase of the contraction can be described by Hill's (1938) equation with the following parameters (at 37 degrees tc): a/Po = 0.73 plus or minus 0.04, b = 0.54 plus or minus 0.04 lengths/s, Vmax = 0.74 plus or minus 0.02 lengths/s (n = 7, mean plus or minus S.E,). The force-velocity relation of the portal vein in comparison with other kinds of muscle is discussed.
The time course of relaxation under isometric and isotonic conditions was studied in preparations of rat portal vein which maintained regular phasic contractions in solutions with increased [K-+] and [Ca-2+]. It was found that the smooth muscle during isotonic lengthening was able to carry the afterload for a period of time which was longer than expected from the control isometric response. The difference was largest for afterloads corresponding to about half the isometric peak force. The terminal decline in force was identical in afterloaded and purely isometric responses. Inhibitory influences of isotonic shortening causing increased rates of relaxation, as reported for striated muscles, were not observed. The differences in the course of relaxation between isotonic and isometric responses of portal vein could not be attributed to variations in membrane excitation. It also appears that the differences are not due to changes in release or uptake of activator calcium, or to presence of viscous elements in the tissue. It is suggested that the ability of the smooth muscle to carry load over a relatively long period during isotonic relaxation may be attributed to the characteristics of the instantaneous force-velocity relations in the force range above Po.
The possible relationship between changes in electrical and mechanical activity and in tissue levels of cyclic AMP (cAMP) during relaxation of the myogenical active rat portal vein has been elucidated in response to different inhibitory stimuli. Isoproterenol, 10(-5) M, caused an initial pronounced inhibition of spike discharge and contractions followed by a partial recover over the 15 min exposure period. This inhibitory response was associated with doubling of tissue cAMP after 1 min and a less pronounced increase in later measurements (5 and 15 min). Papaverine, 10(-4)M, caused, in contrast, an inhibition of electrical and mechanical activity which developed gradually over the entire 15 min exposure period. The levels of cAMP at 1,5 and 15 min all exceeded the corresponding values obtained with isoproterenol. The two drugs in combination gave a biphasic inhibitory response associated with a sustained large increase in the level of cAMP. These drug induced inhibitions were thus accompanied by increased levels of cAMP, but the different time courses of the electromechanical responses could not be rlated to corresponding variations in the content of cAMP. Hyperosmolality (+150 mM sucrose) and mechanical vibration (100 Hz) elicited differentiated inhibitions of smooth muscle activity without changes in tissue cAMP. The mechanical effects elicited by isoproterenol, papaverine and hyperosmolality were accompanied by approximately parallel changes in electrical spike discharge. It is concluded that increased levels of cAMP are not indispensible for vascular smooth muscle relaxation, and that the magnitude of pharmacologically induced inhibitions are not always closely related to the total tissue content of the nucleotide.
The spontaneous electrical and mechanical activity of the isolated rat portal vein is abolished after only 2-3 min in nominally Ca-free medium, and after 5-6 min there is no contractile response to depolarizing (122 mM K+), Ca-free solution. In the present study we have examined the electrical and mechanical responses of the portal vein to depolarization with simultaneous readministration of Ca2+ (2.5 mM) after periods of variable length in Ca-free standard solution. After 30 to 60 min of Ca depletion a slow contracture occurred in response to the high-K+ solution with 2.5 mM Ca2+. When the period in Ca-free medium was reduced below 30 min an early, faster phase appeared in the contracture response, and this phase was more rapid the shorter the time of Ca depletion. It is suggested that the slow contracture obtained after 30 min or more uses mainly extracellular Ca for activation and that the faster phase seen after shorter periods of Ca depletion is due to release of superficially bound Ca. This latter pool of tissue bound Ca does not alone produce contraction in response to depolarization, suggesting that extracellular Ca is required to trigger the release perhaps through a regenerative process.
The effects of static and dynamic passive stretch and shortening on electrical activity and active force were analyzed in the isolated rat portal vein. Static stretch by 40% of muscle length evoked moderate excitatory effects with enhanced mechanical activity and an average increase in spike discharge of 12% above the control value of 55 plus or minus 2.6 spikes/min. The dynamic responses studied at various rates of length change (dL/dt) over the range between minus 12 and plus 12 mm/min, i.e., minus 3 and plus 3% muscle length/sec, were much more pronounced. Active force and spike activity showed graded increases with increasing rates of stretch. The electrical activity reached a value of 180 spikes/min (approximately equal to 325% of control) at 5 mm/min; this frequency was then maintained for stretch rates up to 12 mm/min. Mechanical activity during stretch was further reinforced by the shift along the length-tension diagram. Passive shortening at rates from minus 1 to minus 12 mm/min caused graded decreases in mechanical and electrical activity below the control levels, complete inhibition being observed at the latter dL/dt. Blockade of alpha and beta receptors indicated that the responses were myogenic in nature. The findings seem to provide direct support for the myogenic hypothesis of vascular tone and responses to stretch of the vascular wall, but they indicate that emphasis should be placed on the dynamic characteristics of the stimulus rather than its static nature. This emphasis constitutes a new concept in the myogenic control of the peripheral circulation.
Albumin, transferrin and immunoglobulins A, G and M were determined in both serum and urine from 84 patients with uroepithelial tumours. There were 76 patients with bladder tumours, of which 19 had previously received radiotherapy and 51 were untreated, whereas the remaining 6 had required a urinary diversion with nephrostomy or cutaneous ureterostomy because of ureteric tumour obstruction. Eight patients with tumours situated in the renal pelvis or ureter were examined, seven of these eight patients could be examined both before and after surgical treatment. The changes in urinary protein patterns were compared with the results of various types of treatment of uroepithelial tumours. A significant reduction in urinary proteins was seen after successful treatment, or when the urinary flow was diverted so that it had no tumour contact.
Concentrations of albumin, transferrin and immunoglobulins A, G and M were determined in both serum and urine from 59 patients with uroepithelial tumours. 51 patients had tumours in the bladder, which could be classified according to size, clinical stage and grade of malignancy, the remaining 8 had tumours in the ureter or renal pelvis. Urinary proteins were found in all the patients studied, the concentration being proportional to the tumour size. There was no correlation, however, with the grade of malignancy. The level of serum proteins and the urinary protein fraction pattern were similar in all groups of patients. Immunoglobulins were found in relatively large amounts in the urine, except for IgM which was absent in 13 patients. It is suggested that there immunoglobulins originate from the tumour surface and may represent an immune reaction by the host against the tumour. Their estimation in the urine may be a useful diagnostic help when urinary tract tumours are suspected.