Structurally reduced compliance of the venous capacitance vessels in spontaneously hypertensive rats (SHR).
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Biomedical subjects
Publications and source records attributed to H Nilsson.
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The acute effects of propranolol, 1 mg/kg i.v., were studied in chloralosed, vagotomized cats. The vascularly isolated but innervated calf muscles were perfused from another animal. In one group of experiments, the carotid baroreceptors were exposed to ambient arterial pressure. Here, propranolol caused a fall in heart rate and an increase in resistance of the isolated muscle bed. In other experiments, the carotid sinuses were perfused at a constant pressure. In these animals, no increase in muscle flow resistance was observed after the drug. It is concluded that the increase in total peripheral resistance, seen initially upon propranolol administration, may be reflexly induced via the baroreceptors.
Half lobes of mouse thyroid gland were incubated in vitro with TSH. They released cyclic AMP (cAMP) into the medium in amounts depending on the concentration of TSH. The release of cAMP was greatest during the first hour of incubation then it occurred at a lower rate. With an incubation time of 45 min the medium cAMP levels ranged from 43.0 +/- 11.9 pmole per mg tissue protein for controls to 296.5 +/- 29.2 pmole per mg tissue protein with 5 mU of TSH in the medium. The tissue cAMP level reached a maximum after 15--30 min of incubation with TSH, then it gradually decreased towards control level during 4 h of incubation. With 25 min of incubation the tissue cAMP level was 28.5 +/- 8.8 pmole per mg tissue protein for controls compared to 194.3 +/- 27.0 pmole per mg tissue protein with 5 mU TSH in the incubation medium. The release of thyroxine was of the same order during the later part of the 4 h incubation period compared to the first one. The results illustrate the quantitative importance of cAMP release, and the fact that in the later part of the incubaion period the cell content of cAMP was low while the release of thyroxine remained high.
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Human lymphocytes treated with the plant protein concanavalin A are stimulated to transform into blasts, without developing cytotoxicity for chicken erythrocytes. Prior treatment of lymphocytes with concanavalin A potentiated phytohemagglutinin-induced blast transformation and DNA synthesis but completely inhibited phytohemagglutinin-induced cytotoxicity. Inhibiton was not due to suppression of the mixed lymphocyte-erythrocyte aggregation normally caused by phytohemagglutinin. Inhibition of cytotoxicity was reversible when concanavalin A was removed from the lymphocytes by treatment with methyl-alpha-D-manno-pyranoside after 1 hour but not after 20 hours. The results indicate that blast transformation and cytotoxicity are separate expressions of lymphocyte stimulation.
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The associations among autonomic neuropathy, urinary albumin excretion, and glomerular filtration rate (GFR) measured with 51Cr-EDTA and iohexol clearance were studied in 41 patients with insulin-dependent diabetes mellitus (IDDM) and 15 patients with non-insulin-dependent diabetes mellitus (NIDDM). The study showed that increased urinary albumin excretion was more common in NIDDM than in IDDM. In contrast with IDDM, albuminuria in NIDDM was not related to GFR. Autonomic neuropathy was common in IDDM as well as in NIDDM, and also in patients without nephropathy, but was not connected with hyperfiltration. Low brake index, an ortostatic autonomic index, was associated with nephropathy in NIDDM. Iohexol, a non-ionic contrast medium, was found to be a useful alternative to 51Cr-EDTA for determination of GFR. Moreover, comparison between conventional four-sample plasma clearance and single-sample clearance showed a close correlation. Accordingly, assessment of GFR using a single plasma sample provides reliable results even at high GFR values.
We have investigated the effect of intracellular calcium levels for membrane potential during noradrenaline application in isolated small arteries. Rat mesenteric small arteries were mounted for isometric tension measurement. Smooth muscle membrane potentials were measured by conventional intracellular electrodes, and intracellular calcium concentration was measured using Fura-2 fluorescence. Under control conditions, noradrenaline caused contraction and depolarization from -55.5 to -29.3 mV. In intact arteries, depleting intracellular calcium stores with thapsigargin caused smooth muscle hyperpolarization and inhibited contraction to noradrenaline. In de-endothelialized vessels, thapsigargin still depleted calcium stores, but did not affect either the depolarization or contraction caused by noradrenaline. In noradrenaline-activated vessels, inhibition of calcium influx by amlodipine caused tension and calcium levels to fall to near-baseline levels, but membrane potential returned by only 55%. Treatment with a combination of thapsigargin, D-600 and BAPTA-AM inhibited the tension and calcium responses to noradrenaline, but the membrane potential response was reduced by only 34%. Acute reduction of extracellular chloride concentration caused similar, small depolarization at rest and during noradrenaline exposure. It is concluded that an elevation of intracellular calcium concentration is not essential for noradrenaline depolarization, although part of the depolarization is associated with the raised intracellular calcium level.
The concentration dependence of ATP-induced contractions in isolated resistance arteries was estimated using photolysis of caged ATP. Rat mesenteric vessels were isolated and mounted for force registration in a small chamber allowing illumination from a xenon-flash lamp. Photolysis of 100 microM caged ATP, which released about 20 microM ATP within a few milliseconds in the vessel, induced a transient contraction with an amplitude approximately 40-50% of the response induced by 10 microM noradrenaline. The responses could neither be induced by the light flash as such nor by caged ATP alone nor by photolysis of caged phosphate. The amplitude of the contractions was dependent on the concentration of caged ATP, and the effective concentration for ATP was estimated to be in the range of 1-10 microM. In contrast, when ATP was introduced by diffusion, about a 100-fold higher concentration was required. Thus photolytic release of ATP minimizes metabolism before its action on receptors and reveals action of ATP in a concentration range consistent with a role of ATP as a transmitter in nervous regulation of the tone of resistance vessels.
The role of membrane potential-dependent and independent regulation of the intracellular free calcium concentration ([Ca2+]i) was assessed in the mesenteric small arteries of Wistar rats. [Ca2+]i was determined by Fura-2 fluorescence. Membrane potential measurements were made using intracellular microelectrodes. Depolarization with a high-potassium solution (K-PSS) elevated [Ca2+]i and induced contraction. Further addition of 10 microM noradrenaline (NA) did not elevate [Ca2+]i further but enhanced tone. Addition of calcium channel inhibitors (felodipine or D-600) inhibited the maintained rise in [Ca2+]i with K-PSS, but NA still elevated [Ca2+]i and force to about half the previous level. Further addition of either ryanodine or thapsigargin eliminated the rise in [Ca2+]i with NA, although 10-20% of the contraction remained. Simultaneous measurements of membrane potential, [Ca2+]i, and force during cumulative additions of NA or K-PSS in the absence of inhibitors showed similar relations between membrane potential and [Ca2+]i for each means of activation. The results indicate that membrane potential and [Ca2+]i are strongly correlated in mesenteric small arteries. A small part of the [Ca2+]i increase to NA can be attributed to release from intracellular stores. Membrane potential-independent calcium channels that are directly operated by adrenoceptors appear to play a minor role in the regulation of [Ca2+]i in these vessels.
The effects of 30 minutes of exposure to ouabain on calcium sensitivity have been investigated in two types of resistance vessels from 12 pairs of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Branches of the superior mesenteric and femoral arteries, with internal diameters of about 200 micrometer, were mounted as ring preparations in a myograph capable of measuring their isometric wall tension. Dose-response curves for calcium upon norepinephrine stimulation were determined under conditions where neuronal uptake was eliminated. Initially, when stimulated with norepinephrine, the SHR vessels from both locations were more sensitive to calcium and had stronger contractions than their controls. The addition of ouabain (1 mM) to the relaxed vessels immediately elicited a moderate, transient contraction in the branches of the femoral artery, whereas no response was observed in the mesenteric vessels. Although the addition of ouabain to activated vessels produced an immediate potentiation of the response, prolonged (30-minute) exposure to ouabain reduced active tension development upon norepinephrine stimulation in all vessels. The reduction was greatest in the SHR vessels, so that, under these conditions, the norepinephrine-activated calcium sensitivity of corresponding SHR and WKY vessels was similar. By contrast, responses to norepinephrine in high potassium solution were unaffected. The results suggest that under normal conditions, SHR vessels may have a specific increase in the permeability of the norepinephrine-activated calcium channels. Prolonged exposure to ouabain appears to reduce the permeability of these channels, providing an explanation for why this treatment eliminates the difference in calcium sensitivity of the SHR and WKY vessels.
The influence of flip angle and TR on signal to noise ratio and contrast between cerebrospinal fluid (CSF) and cord was evaluated in cervical spine imaging in 5 volunteers, using gradient echo technique. All experiments were performed on a 0.3 tesla Fonar beta-3000 M scanner using solenoidal surface coils. The most useful sequence was considered to be TR/TE = 300/12 ms and 10 degrees flip angle. This sequence provided images with a 'myelographic appearance' with good delineation of cord, CSF and epidural space. The grey and white matter was also regularly visualized. The acquisition time was considerably shorter than would have been necessary if a long TR/TE spin echo sequence had been used to obtain the same contrast pattern and the sequence was not as sensitive to motion as was the spin echo sequence. The sequence was also evaluated in 10 patients with degenerative disease and in 5 with lesions in the cord. The gradient echo sequence was found to be equal to or better than short and long TR/TE spin echo sequences in demonstrating narrowing of the spinal canal and cord lesion. The drawback is the limited signal to noise ratio.
In order to optimize the coil selection for cervical and thoracic spine imaging the signal characteristics of two different solenoidal surface coils (15 cm and 30 cm diameter, respectively) as well as the head coil and body coil were determined using a 0.3 T MR scanner with a vertical magnetic field. Signal-to-noise ratio curves were obtained for each coil using tube phantoms and a human-like phantom. The findings were compared with images obtained in two healthy volunteers. The head coil was found to be superior for imaging of the cranio-cervical junction while the 15 cm surface coil gave better results in the remaining part of the cervical spine and the upper thoracic spine. The body coil was superior for imaging of the thoracic region at the level of the shoulders (T4-T6) but the 30 cm surface coil was better for the more caudal part of the thoracic spine. Combined phantom and in vivo studies are also recommended for evaluation of future, improved coils.