Search PubMed⌕ Search

Biomedical subjects

P Hellstrand

Publications and source records attributed to P Hellstrand.

82 records · Page 5Linked to original sources
PubMed1978

Responses of smooth muscle to quick load change studied at high time resolution.

Quick-release and quick-stretch experiments have been performed on preparations of smooth muscle from rat portal vein and rabbit urinary bladder. The low equivalent mass of the isotonic lever (8 mg) implied that inertial oscillations were limited to the first 5-10 msec after the load step. The high time resolution achieved in this way enabled us to separate three components in the length response to a step change in force: (1) an immediate passive elastic recoil, (2) an isotonic velocity transient lasting 50-75 msec and (3) shortening of the contractile element after its full adjustment to the new load. The maximal series elastic recoil was about 10% of the total muscle length in portal vein but only some 3% in urinary bladder. Stiffness of series elasticity increased in proportion to force and was about 3 times higher in bladder than in portal vein at any force level. Force-velocity relations for loads less than Po could be fitted to Hill's equation; Vmax in 4 AC-stimulated portal veins was 0.53 +/- 0.03 muscle lengths/sec and in 8 K+-activated bladder preparations 0.18 +/- 0.01 muscle lengths/sec. Application of loads greater than Po produced rates of lengthening greater than expected from an extrapolation of Hill's hyperbola. The nature of the transient component is discussed in the light of recent studies of force and velocity transients in skeletal muscle.

Animals↗
PubMed1977

Mechanical, electrical, and biochemical effects of hypoxia and substrate removal on spontaneously active vascular smooth muscle.

Effects of hypoxia and glucose-free solution on the isolated rat portal vein were studied. Decrease of extracellular PO2 below 50 mm Hg caused graded inhibition of spontaneous mechanical activity; below 7 mm Hg, inhibition was complete in most preparations. Contracture force of depolarized portal vein was less sensitive to decreases in PO2. Responses to noradrenaline at all concentrations were markedly depressed at extreme hypoxia. Sucrose-gap experiments showed that hypoxia reduced the spontaneous electrical spike discharge. Mean tissue contents of PCr, ATP and glycogen (expressed as glucose) were 3.02, 2.47 and 5.07 micromol/g cell wt. in spontaneously active control muscles and 1.07, 1.65 and 1.83 after 20 min anoxia. Physiological variations in PO2 may influence myogenic activity of vascular smooth muscle largely through an action at the membrane level and this mechanism may participate in local blood flow control. Caculations indicated that the graded response to hypoxia in the present in vitro experiments was not due to diffusion limitation. Spontaneous mechanical activity was relatively well maintained even after prolonged exposure to glucose-free solution, whereas the responses to K+ and noradrenaline were markedly suppressed. Electrophysiological recordings during spontaneous activity indicated desynchronization and impaired conduction. PCr and ATP were maintained at control levels and glycogen reduced by 50 per cent after 2 h in glucose-free medium. Indications of the use of amino acids (glutamate) as substrate under these conditions were obtained.

Action Potentials↗
PubMed1977

Oxygen consumption and lactate production of the rat portal vein in relation to its contractile activity.

Energy turnover in the isolated rat portal vein was investigated by measurement of oxygen consumption (JO2) and lactate production (JLA) under simultaneous recording of mechanical activity. In spontaneous activity under aerobic conditions and at optimal muscle length JO2 and JLA were 0.55 and 0.62 micromol/min X g, respectively, corresponding to an ATP-production of 4.3 micromol/min X G. When muscle length was changed, an approximately linear relation was found between energy turnover and mean isometric tension. The tension-indpendent part of ATP-production was 3.0 micromol/min X g. In Ca2+-free solution the metabolic rate was 20% lower still. JO2 was nearly equal in isometric contractions and in afterloaded isotonic contractions from the same initial muscle length. During a maximal tonic contracture in 5+-depolarized portal vein JO2 increased to about twice that in spontaneous activity. Changes in contracture force by variations in muscle length or in [Ca2+]0 were associated with identical linear relations between JO2 and active tension. This relation was less steep than the corresponding relation for spontaneous activity. The anaerobic lactate production of the portal vein was 2.7 times theaerobic leve. The accelerated glycolysis did not compensate for eliminated oxidative metabolism. Under substrate-free aerobic conditions no lactate was produced by the muscle and compared to the control situation JO2 declined more than could be accounted for by reduced mechanical activity alone. The metabolic turnover rate in relation to isometric tension is high in the rat portal vein compared to that of tonic vascular smooth muscle from larger vessels. This correlates with differences in dyanmic mechanical properties. At comaparable tension levels in the portal vein, the rate of cross-bridge turnover may be higher in spontaneous phasic activity than in sustained contracture.

Adenosine Triphosphate↗
PubMed1975

The force-velocity relation in phasic contractions of venous smooth muscle.

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.

Animals↗
PubMed1975

Isometric and isotonic relaxation in venous smooth muscle.

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.

Action Potentials↗
PubMedDate not supplied

Increased store-operated Ca2+ entry into contractile vascular smooth muscle following organ culture.

Ca2+ inflow via store-operated Ca2+ channels was investigated in rings of rat tail and basilar arteries kept in serum-free organ culture, which is known to preserve the contractility of the vascular smooth muscle. After culture for 3-4 days, Ca2+ release from intracellular stores in response to caffeine (20 mM) was augmented 2- to 4-fold. Following depletion of intracellular Ca2+ stores by caffeine and thapsigargin (10 microM), addition of Ca2+ (2.5 mM) caused an increase in the intracellular Ca2+ concentration which was 2-3 times greater in cultured than in freshly dissected rings, and was not affected by verapamil (10 microM). In contrast, L-type Ca2+ channel currents were decreased by 20% after culture. While freshly dissected rings developed no or very little force in response to the addition of Ca2+ after store depletion, cultured rings developed 42% (tail artery) and 60% (basilar artery) of the force of high-K+-induced contractions. These contractions in cultured vessels were insensitive to verapamil but could be completely relaxed by SKF-96365 (30 microM). Store depletion by caffeine increased the Mn2+ quench rate 3- to 4-fold in freshly dissected as well as cultured tail artery, while there was no increase in freshly dissected basilar artery, but a 3-fold increase in cultured basilar artery. Uptake of Ca2+ into intracellular stores was twice as rapid in cultured as in freshly dissected tail artery. This study shows that organ culture of vascular smooth muscle tissue causes changes in Ca2+ handling, resembling the pattern seen in dedifferentiating smooth muscle cells in culture, although contractile properties are maintained.

Animals↗
PubMedDate not supplied

Effect of glibenclamide on membrane response to metabolic inhibition in smooth muscle of rat portal vein.

Vascular smooth muscle tone is dependent on oxidative metabolism, a phenomenon of potential importance for the metabolic regulation of blood flow to tissues. The response of the rat portal vein to inhibition of cell respiration by cyanide (0.1-1 mM) is a reduction of its spontaneous myogenic activity. The trains of action potentials triggering phasic contractions are reduced in duration, while the frequency of trains is often somewhat increased as the resting membrane potential in the intervals between spike trains is less negative by 6.5 mV. Glibenclamide (10(-7) M) did not affect the resting membrane potential or spontaneous mechanical activity of oxygenated portal veins, but partly restored the depressed myogenic activity in the presence of cyanide (0.5 mM). The spike trains were longer, while the membrane was depolarized by 3 mV compared with the effects of cyanide alone. Inhibition of both oxidative and glycolytic metabolism by 2 mM NaCN in a medium where glucose was replaced by beta-hydroxybutyrate caused a hyperpolarization which was abolished by 10(-7) M glibenclamide. The relaxing effect of the K+ channel opener cromakalim (5 x 10(-9) to 6.25 x 10(-7) M) was partly antagonized by glibenclamide. Basal cytosolic [Ca2+] was increased by cyanide, while the Ca2+ transients associated with phasic contractions were reduced in duration. This latter effect was partially reversed by glibenclamide. The effect of cyanide on high-K+ contractures, which are associated with sustained membrane depolarization and not dependent on repetitive spike activity, was not influenced by 10(-7) M glibenclamide. The effects of inhibited cell respiration on spontaneous electrical activity seem to reflect a depolarizing drive caused by inhibited active ion exchange mechanisms, modified by a repolarizing drive, possibly from ATP-regulated K+ channels, causing reduced duration of the spike trains. While glibenclamide affects spontaneous activity at all levels of oxidative blockade, glibenclamide-sensitive hyperpolarization is seen only when both oxidative and glycolytic metabolism is inhibited.

Animals↗
PubMedDate not supplied

Inhibition of calcium entry preserves contractility of arterial smooth muscle in culture.

The addition of the growth stimulator fetal calf serum (FCS, 10%) to rings of rat tail artery causes an increase in [Ca2+]i, accompanied by contraction. This response was inhibited by the calcium entry blocker verapamil (1 microM). To investigate the effect of Ca2+ entry blockade on growth and contractility, rings of rat tail artery were cultured for 4 days in medium with or without FCS and then mounted for tension registration and stimulated with noradrenaline (NA) or high-K+ solution. In cultured rings growth was quantitated by [3H]-thymidine incorporation and increase in protein contents. FCS in the medium stimulated DNA synthesis by about 2-fold and increased protein contents by about 70%. The growth-stimulated cultured rings developed less force than freshly prepared rings (2.2 +/- 0.3 vs. 8.3 +/- 1.0 mN/mm). The addition of 1 microM verapamil to the medium during culture increased maximal NA-evoked force to 5.0 +/- 0.4 mN/mm but had no effect on the increases in DNA synthesis and protein contents. Force developed by growth-arrested rings, cultured in the absence of FCS, was not different from that of freshly prepared rings (7.2 +/- 0.6 mM/mm). Verapamil did not affect maximal force in these rings. Similar responses were seen when contraction was elicited by high-K+ solution. We conclude that verapamil, present during culture, preserves contractility of arterial smooth muscle, and that this effect is not parallel to inhibition of growth.

Animals↗