PubMed Health⌕ Search

Biomedical subjects

N L Stephens

Publications and source records attributed to N L Stephens.

At least 109 records · Page 6Linked to original sources
PubMed1985

Smooth muscle contractility. Effects of hypoxia.

Mechanical perturbation of smooth muscle provides information about the mechanical properties of its crossbridges. We have developed a method for identifying: (1) that normally cycling and very slowly cycling are sequentially activated, (2) the moment of this transition, and (3) the proportions of the two types of bridges recruited. Hypoxia decreases muscle shortening ability before isometric force. The former is due to depression of activity of both types of bridges.

Animals↗
PubMed1984

Pharmacological properties of canine intrapulmonary blood vessels.

The contractile response of ring segments of large, medium, and small pulmonary arteries and veins of the dog to histamine, norepinephrine, and serotonin have been studied. The maximum contractile response to these drugs was normalized with respect to the maximal response obtained in stimulation with 127 mM K+. The small pulmonary artery was more reactive to histamine, norepinephrine, and serotonin when compared with large and medium pulmonary arteries. The medium and large pulmonary artery showed no difference in reactivity to histamine. However, the mean effective dose (ED50) values for these agonists among the different segments of pulmonary arteries showed no significant difference. The small and medium pulmonary veins demonstrated increased reactivity to histamine, but not norepinephrine and serotonin. The ED50 values also indicated that both small and medium veins were more sensitive to histamine when compared with the large pulmonary vein. The log concentration percent response curves for both small and medium pulmonary veins were displaced leftward (increased sensitivity) with respect to that for the large pulmonary vein. However, the reactivity and sensitivity to histamine between medium and small pulmonary veins were no different. The reactivity and sensitivity of different segments of pulmonary veins to norepinephrine and serotonin showed no significant differences among them. We conclude that histamine and other vasoactive substances, which are directly or indirectly related to mast cell degranulation, exert pharmacological effects on the pulmonary vasculature which possesses differential responsiveness at various levels of the vascular tree.

Animals↗
PubMed1983

Maximum shortening velocity of smooth muscle: zero load-clamp vs. afterloaded method.

Previous reports from this laboratory of force-velocity relationships of canine tracheal smooth muscle (TSM) have presented maximum shortening velocities (Vmax) mathematically derived from the linearized transformation of the Hill equation (A. V. Hill, Proc. Roy. Soc. London, Ser. B., 126:136-195, 1938). Recent technical advances enable us to measure Vmax directly using an electromagnetic lever system that can instantaneously clamp to a zero load, thus we compared values of Vmax derived mathematically and those directly measured on the same TSM strips. Derived Vmax values from afterloaded isotonic shortening curves for loads greater than preload were 0.328 +/- 0.021 optimal length (lO)/s and were not significantly different from zero load-clamp measurements of 0.301 +/- 0.022 lO/s from the same (n = 15) muscles. These data indicate that Vmax values mathematically derived for TSM from conventional isotonic afterloaded force-velocity curves are valid estimates of zero load velocity, because they were not significantly different from values obtained by direct measurement using the zero load-clamp technique.

Animals↗
PubMed1983

Mechanical properties of pulmonary arteries from sensitized dogs.

On the basis of isometric dose-response studies, we (J. Pharmacol. Exp. Ther. 219:551-557, 1981) have reported that the ovalbumin-sensitized (S) canine pulmonary artery (PA) is hypersensitive and hyperractive to histamine compared with that from a littermate control (C) in vitro. In this study, our aim was to determine whether the maximal velocity of shortening (Vmax) measured in strips of electrically stimulated SPA and CPA differed. Vmax (velocity at zero load) was obtained by analysis of force-velocity curves from these tissues using the equation (P + a) (V + b) = (Po + a)b, in which P is load, Po is maximum tetanic tension, V is shortening velocity, and a and b are asymptotic values in units of force and velocity. The Vmax values derived for SPA and CPA are 0.188 +/- 0.029 (SE) and 0.113 + 0.017 lo/s, respectively, lo being defined as that length at which Po is obtained. This result indicated that the Vmax value of SPA is significantly (P less than 0.05) different from that of CPA. The b values for SPA [0.034 +/- 0.003 lo/s] and for CPA [0.025 +/- 0.004 lo/s] were also significantly different. However, the force constants a and Po were unchanged in the SPA and CPA. SPA also had a greater isotonic shortening capacity than CPA. These findings indicate that mechanical properties of SPA are altered and lend an understanding of the hyperreactivity of these vessels in the sensitized model.

Animals↗
PubMed1982

Maximal force potential of tetanized mammalian smooth muscle.

By applying abrupt load clamps of varying magnitude at a given moment during the course of an isotonic tetanus in smooth muscle of canine trachea (TSM) and saphenous vein (CSV), it is possible to obtain a measure of the maximal load-bearing capacity of the force-producing sites in these muscles. This capacity has been termed maximal force potential (MFP). By applying such load clamps at differing times throughout the course of the tetanus and beyond, we have been able to obtain MFP curves for TSM and CSV. MFP curves for these smooth muscles differ from those for striated muscle. First, although MFP in striated cardiac muscle is only about 20% greater than tetanic force, it is up to nearly 200% greater in smooth muscle. Second and more importantly, although in striated muscle MFP curves return to zero along with the tetanic force curves, in smooth muscle MFP is maintained for long after the isometric tetanus has returned to zero.

Animals↗
PubMed1981

Relaxation of tetanized canine tracheal smooth muscle.

As is the case for striated muscle, relaxation in smooth has been little studied and is less understood. We report studies of load bearing capacity during relaxation of airway smooth muscle. The model employed was the canine tracheal smooth muscle (TSM). The effect of load on the time course of relaxation was analyzed either by comparing afterloaded contractions against various loads or by imposing abrupt alterations in load (load clamps). Unlike mammalian cardiac muscle in which relaxation was reported sensitive to loading conditions, relaxation in TSM was largely independent of loading conditions. In this it resembled frog heart muscle and mammalian cardiac muscle cells without functioning calcium sequestering systems. This type of relaxation which is not influenced by manipulation of loading conditions, has been termed "inactivation-dependent' relaxation. It appears to operate in muscle tissue in which the calcium sequestering apparatus is poorly developed and the dissipation of activation (removal of activating calcium, detachment of force generating sites, etc.) appears to be the rate limiting step during relaxation.

Animals↗
PubMed1981

Relaxation of tetanised smooth muscle of canine saphenous vein.

Since vascular filling depends on the cross-sectional area of the venous bed and since this is determined by the state of relaxation of the mural smooth muscle, we have studied load bearing capacity during relaxation of the smooth muscle of canine saphenous vein. The effect of load on the time course of relaxation was analysed either by comparing afterloaded contractions against various loads or by imposing abrupt alterations in load (load clamps). Unlike mammalian cardiac muscle in which relaxation was reported sensitive to loading conditions, relaxation in the smooth muscle of the saphenous vein was largely independent of loading conditions. In this it resembled frog heart muscle. This type of relaxation, which is not influenced by manipulation of loading conditions, has been termed "inactivation-dependent" relaxation. It appears to operate in muscle tissue in which the calcium sequestering apparatus is poorly developed and sequestration or some process downstream to it appears to be the rate limiting step during relaxation.

Animals↗
PubMed1981

Mechanics and energetics of lengthening of active airway smooth muscle.

For smooth muscle in general there appears only one report dealing with force-velocity (FV) relationships of active muscle subjected to forcible elongation by application of loads (P) greater than its maximum isometric tetanic tension (Po); for airway smooth muscle (ASM) there is none. Since ASM may be subjected to increasing stretch during inspiration, the relationship is important and was therefore studied with canine tracheal smooth muscle (TSM) as a model. FV data for P less than Po could be fitted by Hill's hyperbolic equation. For P greater than Po, lengthening velocity was greater than predicted by the equation. However at equivalent velocities, the muscle during elongation could support a load three times greater than during shortening; in this it resembled skeletal muscle. From this it may be speculated that distension of the airway during inspiration would not be associated with mechanical instability. With reference to energy requirements of the elongating TSM it was shown, as has been for skeletal muscle, that the net rate of energy liberation (assessed by measuring tissue levels of adenosine triphosphate and creatine phosphate) in an elongating active muscle is less than that of a muscle contracting isometrically.

Adenosine Triphosphate↗
PubMed1981

Pharmacological studies of sensitized canine pulmonary blood vessels.

Pulmonary artery and vein from an ovalbumin sensitized canine model of allergic asthma showed hypersensitivity (leftward shift of dose-response curve) and hyper-reactivity (upward shift) to histamine when compared to those from a littermate control in vitro. Dose-response studies showed that only sensitized pulmonary veins exhibited hypersensitivity, but not hyper-reactivity, to norepinephrine. However, sensitized pulmonary arteries showed neither hypersensitivity nor hyper-reactivity to norepinephrine. Both sensitized and control pulmonary arteries and veins displayed no difference in serotonin dose-response curves. The Schultz-Dale reaction was only observed in the sensitized pulmonary veins; it could be blocked (25-45%) by pyrilamine maleate (10(-7) M) and (5-15%) by phentolamine (5 X 10(-6) M). We concluded that anaphylaxis develops only on the venous side of the pulmonary circulation, but that increase in sensitivity or reactivity to agonists develops in both arteries and veins. Histamine appears to be the major, but not the only, mediator released and we have obtained data to suggest it exerts its contractile effect on the muscle via both postsynaptic (directly) and presynaptic (indirectly) effects.

Anaphylaxis↗
PubMed1980

Histamine pharmacology in airway smooth muscle from a canine model of asthma.

Tracheal smooth muscle (TSM) from an ovalbumin sensitized canine model of allergic asthma showed hypersensitivity and hyper-reactivity to histamine (H) when compared to that from littermate controls in vitro. Mepyramine abolished H responses in TSM of both groups; it also abolished the allergic response to obalbumin of TSM from sensitized dogs. The H2 receptor agonist, 4-methyl histamine (4-MH) caused small dose-related decreases in H contractures but had no effect on carbachol- or K+-induced tension. Metiamide, an H2 antagonist, did not enhance the H contracture, suggesting the 4-MH may not be exerting a relaxant effect since H2 receptors were absent. The maximum H-induced isometric tension was potentiated when the sensitized and control muscle strips were pre-equilibrated with 4-MH. These observations are consistent with the presence in canine TSM of H1 but not relaxant H2 receptors, the release of endogenous H to the tissue during the antigen-antibody reaction, and the competition of H and 4-MH for the H1 receptors. Experiments with specific blockers also indicated that in this model the only transmitter found in the ovalbumin-induced allergic bronchospasm was histamine.

Airway Resistance↗
PubMed1978

Characterization of frog muscle mitochondria.

Studies on oxidative phosphorylation revealed that, in frog skeletal muscle mitochondria (SKMM) from the thigh, the adenosine diphosphate/oxygen ratio (ADP/O) was 2.8 +/- 0.1 SE, and the respiratory control ratio was 9.5 +/- 0.9, with pyruvate/malate as the substrate. Oxygen uptake rate (Qo2) was 225 mumol O2 per minute per gram mitochondrial protein +/- 13; phosphorylation rate (ADP/O X Qo2 X 2) was 1,230 mumol ADP phosphorylation per minute per gram mitochondrial protein +/- 77; and the phosphorylation capacity (phosphorylation rate times tissue mitochondrial protein content) was 3.6 mumol ADP phosphorylated per gram wet weight of muscle +/- 0.2. Tissue mitochondrial protein content was determined by the measurement of nicotinamide adenine dinucleotide (NADH) oxidase activity. Electron microscopy (EM) revealed intact, isolated, energized twisted mitochondria of a condensed form. Frog sartorius muscle mitochondria gave similar oxidative phosphorylation parameters when investigated independently of the rest of the thigh. These values of SKMM respiration from the frog are similar to those values obtained from pigeon and rabbit heart and rat skeletal muscles. However, because of the low NADH-oxidase activity indicating reduced mitochondrial content (this was verified in low-magnification EM pictures), phosphorylation capacity was significantly reduced in frog skeletal muscle mitochondria.

Animals↗
PubMed1977

Study of reversibility of effects of hypoxia in airway smooth muscle.

We have shown in the past that hypoxia impairs contractile activity in tracheal smooth muscle (TSM). This was associated with partial uncoupling of mitochondria. It remained to be determined whether these changes were reversible. The TSM model was felt to be superior to the isolated mitochondria since it was likely to be free from artefacts inherent in procedures involving homogenisation and extraction. We report here that the oxygen uptake rates of the isolated, mechanically active TSM were increased in the posthypoxia recovery period when compared with the prehypoxia active muscle. Mechanical recovery was complete.

Acetylcholine↗
PubMed1977

Isometric and isotonic contractions in airway smooth muscle.

Canine tracheal smooth muscle was used as an in vitro model of smooth muscle in intrapulmonary airways to determine whether active tension curves derived from isometric and isotonic muscles are similar, and thus resemble striated muscle in this respect. Isometric, isotonic after-loaded, and isotonic free-loaded contractions elicited at different lengths and loads, were analysed. The data demonstrate that length-tension (L-T) diagrams were different in these various types of contractions for electrically and carbachol driven tracheal smooth muscles strips. In general, at any given length active tension is less in isotonic and free-loaded modes of contraction as compared with isometric. We conclude that the ability to actively develop tension at a given length in airway smooth muscle depends on the mode of contraction.

Animals↗
PubMed1977

Mechanical properties of tracheal smooth muscle: effects of temperature.

The effect of temperature on the isometric tetanic myogram was studied in isolated canine tracheal smooth muscle (TSM). At 37 degrees C and 27 degrees C no significant change occurred in maximum tetanic tension (PO). At 17 degrees C a significant reduction was seen Values of Q10 for contraction time (tPO) were almost halved, whereas those for rate of tension development (dP/dt) were almost doubled. The effect of the same temperatures on the force-velocity (F-v) relationships was also studied. All three F-v curves were described by the Hill equation, (P + a) (v + b) = (PO + a)b. Vmax and b decreased with decreased temperature, with Q10's demonstrating they were dependent on active processes. Finally, the decreased dP/dt of the myogram at lower temperatures was felt to be the probable result of decreased contractile element velocity because no decrease in series elastic component stiffness was demonstrable, there being instead an increase in stiffness at lower temperatures.

Animals↗
PubMed1977

Intracellular pH in hypoxic smooth muscle.

Hypoxia impairs contractility in canine tracheal smooth muscle (TSM). This is attributed to intracellular lactacidosis. The present studies were undertaken to confirm this. Lactate was found to be significantly increased in hypoxic TSM (65.36 +/- 7.37 mg/100 g wet tissue), compared to normoxic (29.83 +/- 5.05). Intracellular pH (pHi) was, however, significantly increased in hypoxic active TSM to 7.71 +/- 0.05 as compared to 7.30 +/- 0.03 in normoxic active muscle. pHi of resting normoxic muscle (7.20 +/- 0.04) was statistically not different from that of resting hypoxic muscle. The pHi's of resting normoxic and active hypoxic muscles were significantly different. These results show that under in vitro, hypoxic conditions: 1) an increase in glycolysis in TSM is indicated by the increased lactate production, 2) there is a surprising, concomitant rise in pHi rather than a decrease as previously expected, and 3) it is mechanical activity of the muscle which leads to this paradoxical result, inasmuch as pHi is unaltered in the resting hypoxic muscle.

Alkalosis↗
PubMed1977

Effect of respiratory acidosis and activity on airway smooth muscle intracellular pH.

Previous work in our laboratory has shown that respiratory acidosis (RA) impaired mechanical function in canine tracheal smooth muscle (TSM). Since an intracellular acidosis could be brought on by the increased CO2 content of the bathing medium and alter the Km's of rate-limiting glycolytic enzymes in the pathway of energy production for contractile function, we have investigated the effects of RA on the intracellular pH (pHi) of TSM. Using the DMO method, paired unstimulated or resting TSM strips were incubated under normocapnic conditions (PO2 600 Torr, PCO2 40 Torr, pH 7.40) and RA (PO2 550 Torr, PCO2 110 Torr, pH 6.95) with 14C-labeled DMO and 3H-labeled inulin or PEG-4000. In another set of paired experiments, TSM strips were tetanized electrically every 5 min or pharmacologically throughout the incubation period ("active" muscle strips). The tissue and an aliquot of bathing medium were counted for 3H and 14C content and the values entered into the Wadell and Butler equation. The pHi's of "resting" normocapnic and acidotic strips were 7.041 +/- 0.017 (SE) and 6.752 +/- 0.012, respectively. However, the pHi's of "active" normocapnic and acidotic strips were 7.275 +/- 0.017 and 7.017 +/- 0.015, respectively. We conclude that respiratory acidosis lowers intracellular pH in both resting and mechanically active TSM's; however, "active" preparations whether exposed to normocapnia or acidosis were unexpectedly more alkaline than their "resting" counterparts.

Acidosis, Respiratory↗