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PubMed1989

[Effects of thromboxane A2 synthetase inhibitor, DP-1904 on the action of vasoactive substances in guinea pig trachea and lung tissue strips].

Thromboxane A2 (TxA2) is a potent platelet aggregator and vascular or bronchial constrictor. DP-1904, a newly synthesized imidazol TxA2 synthetase inhibitor, is a potent and long-acting agent. The present investigation was conducted to explore the effect of DP-1904 on the contractile or relaxing responses in guinea pig trachea and lung tissue strips induced by various vasoactive substances. Fourteen guinea pigs, weighing 300-350 g, were sacrificed. Trachea and lungs were removed, cut spirally, set up in bioassay glass jackets and superfused with Krebs-Henseleit solution at 37 degrees C, saturated with oxygen and carbon dioxide. Contraction of tissues was detected by an isotonic transducer and displayed on a polyrecorder. Arachidonic acid-induced relaxing responses in guinea pig trachea strips were attenuated significantly by the continuous infusion of DP-1904 in a dose-dependent fashion. Arachidonic acid-induced contractile responses in guinea pig lung strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Acetylcholine-, histamine- and prostaglandin F2 alpha-induced contractile responses in guinea pig lung and trachea strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. The above results suggest that DP-1904 might be a useful therapeutic agent for the treatment of chronic obstructive lung diseases.

Acetylcholine↗
PubMed1982

Tonic force maintenance with reduced shortening velocity in arterial smooth muscle.

The isotonic shortening velocity of swine carotid media tissues contracting in response to high K+, histamine, norepinephrine, or AC electrical stimulation rapidly increased to a maximum value and then declined to a steady-state level while force was still increasing or steady. The maximum shortening velocity calculated for no external load on the tissue (Vo) also decreased during the course of contractions when active stress remained constant. The fall in velocity with time was not Ca2+ dependent, because reductions in the [Ca2+] in high K+ solutions that significantly reduced the maximum stress (Fo) had no effect on Vo in the steady state. On washout of high K+ solutions, the ability of the tissue to shorten on isotonic quick release fell rapidly to low levels before isometric stress exhibited significant declines. The data indicate that cross-bridge cycling rates are modulated in this tissue. We suggest that this reflects the formation of attached, noncycling cross bridges (termed latch bridges), which constitute an internal load on the contractile system during tonic contractions.

Animals↗
PubMed1995

Modulation of gallbladder contraction by pirenzepine in humans.

OBJECTIVES: The mechanism(s) by which cholinergic innervation modulates gallbladder contraction are not fully understood. To elucidate the role of muscarinic M1 receptors in the mediation of gallbladder contraction, we investigated gallbladder volume reduction, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) responses in humans during cephalic and intestinal phases of a meal under M1 muscarinic receptor blockade with pirenzepine. METHODS: In eight healthy subjects, intraduodenal meal- and in seven subjects, sham feeding-induced gallbladder volume reduction was measured by real-time ultrasonography during saline or pirenzepine administration. Plasma CCK and PP were measured by radioimmunoassay. RESULTS: Pirenzepine partially inhibited gallbladder volume reduction in response to an intraduodenal fatty meal. The integrated gallbladder volume reduction over 120 min was 4462 +/- 445%.min compared with 6879 +/- 279%.min in the saline control group (p < 0.01). Integrated plasma CCK and PP responses were unchanged in the presence of pirenzepine. Pirenzepine abolished sham feeding-induced gallbladder contraction and plasma PP response. Sham feeding with either isotonic saline or pirenzepine infusion did not modify fasting plasma CCK levels. CONCLUSION: M1 muscarinic receptors play an important role in the intestinal and cephalic phases of gallbladder contraction. Plasma CCK response to intraduodenal meal is not influenced by M1 muscarinic receptor blockade with pirenzepine.

Adult↗
PubMed1989

[Effects of thromboxane A2 synthetase inhibitor, DP-1904 on the action of vasoactive substances in rabbit blood vessel smooth muscle preparations].

Thromboxane A2 (TxA2) is a potent platelet aggregator as well as a vascular and bronchial constrictor. DP-1904, a newly synthesized imidazol TxA2 synthetase inhibitor, is a potent and long-acting agent. The present investigation was conducted to explore the effect of DP-1904 on the contractile responses in rabbit pulmonary artery and descending aorta strips induced by various vasoactive substances. Fourteen Japanese albino rabbits, weighing about 3 kg, were sacrificed. Rabbit pulmonary artery and descending aorta were removed, cut spirally, set up in bioassay glass jackets and superfused with Krebs-Henseleit solution at 37 degrees C, saturated with oxygen and carbon dioxide. Contraction of tissues was detected by an isotonic transducer and displayed on a polyrecorder. Arachidonic acid-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904 in a dose-dependent fashion. Prostaglandin F2 alpha-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Angiotensin II-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Norepinephrine-induced contractile responses in rabbit pulmonary artery and descending aorta strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. The above results suggest that DP-1904 might be a useful therapeutic agent for treatment of pulmonary hypertension in patients with chronic obstructive lung diseases.

Animals↗
PubMed2000

Shortening velocity of skeletal muscle from humans with malignant hyperthermia susceptibility: effects of halothane.

The aim of this investigation was to assess the effect of halothane on the velocity of shortening and lengthening of muscle from normal subjects and from patients with malignant hyperthermia susceptibility. Strips were mounted horizontally at optimal length in normal Krebs-Ringer's solution and mechanical parameters were obtained before and after exposure to 3 vol.% halothane. The maximun shortening velocity at zero load (V(max)) was determined by using Hill's characteristic equation. The contraction and relaxation indices were measured under isotonic and isometric conditions: maximum shortening and lengthening velocities (maxV(c) and maxV(r), respectively); isometric peak twitch tension; peak of the positive (+dP/dt(max)) and negative (-dP/dt(max)) twitch tension derivative; ratio R1=maxV(c)/maxV(r) and ratio R2=(+dP/dt(max))/(-dP/dt(max)). In normal muscle, halothane markedly increased V(max), maxV(c) and peak twitch tension by 30+/-10%, 30+/-5% and 40+/-15%, respectively. The maxV(r) values increased concomitantly with the maxV(c) values, such that no change in the ratio R1 was observed. Both +dP/dt(max) and -dP/dt(max) increased such that the ratio R2 did not vary. In malignant hyperthermia susceptibility muscle, halothane induced a significant decrease in V(max) (-30+/-10%) and maxV(r) (-45+/-15%) without changing maxV(c). The decrease in maxV(r) was greater than that of maxV(c), such that the ratio R1 increased significantly. Peak twitch tension and +dP/dt(max) remained unchanged whereas -dP/dt(max) decreased significantly; the ratio R2 increased by 40+/-10%. These results suggest that halothane alters the contractile properties of malignant hyperthermia susceptibility muscle.

Anesthetics, Inhalation↗
PubMed2001

Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase.

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an important source of free radicals in the hypoxic diaphragm. The effects of N-acetylcysteine (NAC; 18 mM), Tiron (10 mM), and the XO inhibitor allopurinol (250 microM) were studied on isometric and isotonic force generation during hypoxia (PO(2) approximately 7 kPa). NAC and Tiron decreased maximal force generation, slowed the shortening velocity, and decreased the power output. Fatigue rate was decreased in the presence of either NAC or Tiron. Allopurinol did not alter the contractility or fatigability of the diaphragm. During hyperoxia (PO(2) approximately 85 kPa), neither NAC nor allopurinol affected the contractility or fatigability of the diaphragm. Thus free radicals play a significant role in diaphragm contractility during hypoxia. Whether antioxidants exert a beneficial or harmful effect on muscle performance depends on the contraction pattern of the muscle. Free radicals generated by XO do not play a role in diaphragm contractility during either hypoxia or hyperoxia.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1974

Effect of stretching on the elastic characteristics and the contractile component of frog striated muscle.

1. The force-velocity relationship and the stress-strain curve of the so-called series elastic component (s.e.c.) of frog sartorius, semitendinosus and gastrocnemius have been determined during shortening against a given force (isotonic quick-release) and at high speed (controlled release): (a) from a state of isometric contraction and (b) after stretching of the contracted muscle. In both cases the muscle was released from the same length: this was usually slightly greater than the muscle's resting length.2. The muscle released immediately after being stretched is able to shorten against a constant force, P, equal to or even greater than the isometric force, P(0), at the same length. When the force P applied to the muscle is reduced below P(0) the velocity of shortening is greater after stretching, and the force-velocity curve is therefore shifted along the velocity axis: the shift is maximal when P is near to P(0) and it decreases rapidly with decreasing P.3. The extent of shortening of the s.e.c. required to make the force fall from P(0) to zero is 50-100% greater when the muscle is released immediately after stretching than when it is released from a state of isometric contraction. This difference is found by using either the controlled release method or the isotonic quick-release method.4. If a time interval is left between the end of stretching and the onset of shortening of the contracted muscle (controlled release method), the length change of the s.e.c., for a given fall of the force, is reduced and approaches that taking place when the muscle is released from a state of isometric contraction.5. Curare does not affect the results described above, indicating that these do not depend on modification of the neuromuscular transmission.6. It is concluded that stretching a contracted muscle modifies temporarily: (a) its elastic characteristics, as shown by the greater amount of mechanical energy released for a given fall of the force at the muscle's extremities, and (b) its contractile machinery, as it is suggested by the change of the force-velocity relationship.

Animals↗
PubMed2000

Possible postsynaptic action of aminoglycosides in the frog rectus abdominis.

The present study was undertaken to investigate the postsynaptic effects of aminoglycosides on contractions evoked by acetylcholine (ACh), KCl, electrical field stimulation (EFS) and Na(+)- and Ca(2+)-free Ringer solution with 0.2 mM Na2 EDTA (NaFCaFR) in the isolated frog rectus abdominis. Neomycin inhibited contraction elicited by ACh, NaFCaFR, and EFS at the higher frequencies (8 and 10 Hz) but not those elicited by KCl and EFS at the lower frequencies (2, 3 and 5 Hz). D-tubocurarine inhibited ACh-induced contractions in a concentration-dependent manner. In addition, drug reduced EFS-evoked contractions to a limited extent. Lower concentrations (10(-5), 5 x 10(-5), 10(-4), 2 x 10(-4) and 3 x 10(-4) M) but not higher concentrations (4 x 10(-4) and 5 x 10(-4) M) of methoxyverapamil exhibited a concentration-dependent inhibitory action on NaFCaFR-induced contractions. Similar inhibitions of the same type of contraction were displayed by aminoglycosides (neomycin, streptomycin, netilmycin, gentamycin and amikacin). These results suggest that in addition to their antagonistic action on nicotinic receptors in the frog rectus abdominis, aminoglycosides may exert stabilizing effects on some functional components contributing to contractions at the membrane.

Acetylcholine↗
PubMed1969

Isotonic lengthening and shortening movements of cat soleus muscle.

1. By supplying pulses to different subdivisions of the ventral nerve roots in rotation it was possible to obtain smooth contractions of cat soleus with low rates of stimulation.2. After contracting isometrically the muscle was subjected to ;step' changes in tension after which it lengthened or shortened isotonically.3. Isotonic lengthening movements usually began relatively slowly but proceeded with increasing velocity; this acceleration was most conspicuous when low rates of stimulation were used.4. At low rates of stimulation the isotonic lengthening movement often continued beyond the length at which the muscle could have generated that tension in an isometric contraction. The muscle then shortened slowly back toward that length.5. Isotonic shortening movements began relatively rapidly, but as shortening continued the movement became slower, and often had an irregular oscillatory course.6. The isotonic movements are discussed in relation to the sliding filament theory of muscle contraction.7. The compliance of the series elastic elements was calculated from the relative amplitudes of the ;step' changes in tension and length. The stiffness of this component increased with increasing muscle tension.

Animals↗
PubMed1985

Post-extra systolic potentiation: influence of calcium and verapamil in rat and rabbit hearts.

The interactions of the inotropic effects of verapamil (0.05-2.0 mumol l-1), calcium (0.33-5.2 mmol l-1) and post extra systolic potentiation (PESP) as induced by paired stimulation were studied in isolated rabbit and rat hearts under isovolumic and isotonic conditions. At low doses of verapamil, contractions were depressed, but those elicited by paired stimulation showed less depression than contractions of the same rate during single stimulation and even exceeded the unpotentiated contractions without verapamil. At high doses of verapamil contractility could not be restored by paired stimulation. Although contractions were restored to control level by an increase in extra-cellular calcium they were still abnormal in the sense that PESP could not be elicited. The excitation-contraction (e-c) uncoupling due to low calcium perfusion could be counteracted by paired stimulation but e-c uncoupling due to high dose verapamil could not be reversed by paired stimulation. Our results support the view that PESP does not only depend on augmented slow channel calcium influx but also on an enhanced calcium shift within the sarcoplasmic reticulum. We are doubtful about the idea that PESP can be used clinically to counteract the negative inotropic effect of high doses of verapamil.

Animals↗
PubMed1996

The influence of subject and test design on dynamometric measurements of extremity muscles.

In the context of broader discussions of clinical dynamometry, earlier reviews have raised concerns about the potential effects of variations in subject factors and test procedures on measurements. None, however, have dealt exclusively with these effects. We therefore reviewed more than 200 articles to evaluate in detail the effects of variations in subject factors and test procedures on measurements. Factors relating to subjects that affected measurements were age, gender, weight, athletic background, disability, and limb dominance. Test conditions that led to variations in measurements were range of movement in which values were obtained, type of contraction or movement (concentric, eccentric, isokinetic, isometric, isotonic), pretest procedures (warm-up and gravity-correction procedures, starting position, stabilization, axes alignment, lever arm length, preload, damp/ramp settings), test conditions (speed, test sequence, rest intervals, feedback), and type of data analysis (the data selected and how they are manipulated). In the majority of the publications, the authors failed to provide sufficient detail for accurate replication of test procedures or for comparison with other studies. We advocate that the factors identified in this review be included whenever measurements obtained with a dynamometer are reported. Effective development of normative data, formation of ratios, comparison of measurements across studies, and relating measurements with other performance criteria (eg, measurements of functional performance) all require descriptions of variables relating to subjects and testing. Similarly, meaningful use of these measurements in clinical practice requires consideration and documentation of these variables.

Humans↗
PubMedDate not supplied

Interactions of serotonin with multiple receptors and neurotransmitters in the guinea-pig isolated colon.

The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the guinea-pig isolated proximal colon were studied and analyzed. A classical organ bath setup was used to measure the longitudinal muscle responses isotonically. 5-Hydroxytryptamine induced concentration-dependent contractions which were preceded by relaxations at low concentrations. By means of the neurotoxin, tetrodotoxin, the muscarinic cholinoceptor antagonist, atropine, and selective 5-HT receptor antagonists, it was shown that the contractions to 5-HT are mediated by 5-HT2A receptors, localized on the smooth muscle, and by 5-HT3 and 5-HT4 receptors, localized on cholinergic nerves. The relaxation was abolished by tetrodotoxin and appeared to be mediated by two 5-HT receptor subtypes; the pharmacological profile of the high affinity 5-HT receptor resembled that of 5-HT2C receptors though it displayed also pronounced differences. Subsequently, it was shown that nitric oxide is the mediator released by lower concentrations of 5-HT, while, at higher concentrations, adenosine triphosphate could be involved as an end neurotransmitter as well. No evidence for a peptidergic neurotransmitter, such as vasoactive intestinal polypeptide, was obtained. Results with two 5-HT analogues confirmed the presence of a dual 5-HT receptor system (high and low affinity) regulating each the release of a different neurotransmitter (nitric oxide and adenosine triphosphate, respectively). The above described results stress the important role of 5-HT as a neurotransmitter involved in gastrointestinal motility.

Animals↗
PubMed1981

Vein contraction and smooth muscle cell extensions as causes of endothelial damage during graft preparation.

Meticulous preservation of the endothelial lining of vein grafts harvested during vascular operations is undoubtedly an important factor in determining patency rates following bypass procedures. Destruction of the vein graft's endothelial lining prior to graft implantation results in a more thrombogenic graft which is essentially a collagen-lined tube. This study used light, transmission, and scanning electron microscopy to investigate effects of various methods of vein graft preparation on endothelial and smooth muscle cells of the dog cephalic vein. Veins were removed and stored in one of three heparinized solutions at 10 C for either five minutes or one hour: autologous blood, Plasmalyte((R)) or Plasmalyte((R)) with 0.6 mg/ml papaverine HCI added. The vein wall was extremely sensitive to dissection, manipulation, or introduction of fixative solutions and reacted to such stimuli with severe contraction which not only diminished the luminal diameter but also resulted in protrusion of endothelial cells into the lumen and formation of cytoplasmic extensions of medial smooth muscle cells. Such cytoplasmic extensions were particularly frequent in the immediate subendothelial area and appeared to be instrumental in elevating, separating, or desquamating the endothelial cell lining. Veins stored in blood alone demonstrated the greatest vessel wall contraction and endothelial cell loss. Veins soaked in Plasmalyte((R))-papaverine solution had the most relaxed and normal appearance with minimal endothelial cell loss. Papaverine-treated veins which were subjected to brief periods of distension at pressures of 100 mmHg or greater demonstrated large gaps between the endothelial lining cells. The results suggest pretreatment with papaverine greatly reduces vein graft endothelial cell loss due to contraction, although such relaxation may be detrimental if vein grafts are subjected to excessive pressure prior to reversal of relaxation.

Animals↗
PubMed1987

Contractile responses to ouabain and potassium-free solution in vascular tissue from renal hypertensive rats.

This study characterizes contractions to ouabain and potassium-free solution in isolated vascular segments from two-kidney, one clip (2-K, 1C) hypertensive rats. Aorta, mesenteric artery, and vena cava from hypertensive rats were more sensitive (lower threshold) to ouabain than those from normotensive rats. Contractions of hypertensive vascular segments to potassium-free solution and to ouabain (10(-3) mol/l) were faster than those in normotensive vessels. Monensin potentiated contractions to ouabain and increased the rate of force development to potassium-free solution to a greater extent in normotensive aortae than in hypertensive aortae. Amiloride, low sodium solution, verapamil and calcium-free solution depressed contractions to ouabain and potassium-free solution in both hypertensive and normotensive aortae. These observations demonstrate augmented responsiveness to ouabain and potassium-free solution in hypertensive blood vessels. Interventions which influence transmembrane sodium and calcium movements altered contractions to ouabain and potassium-free solution. The results are consistent with the hypothesis that vascular cells of hypertensive rats have enhanced sodium pump activity.

Animals↗
PubMed1992

In vivo and in vitro correlation of trachealis muscle contraction in dogs.

Maximal trachealis muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the muscle was evaluated in vitro. In vivo trachealis muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the trachealis muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.

Animals↗
PubMed1995

Spontaneous tone in different types of longitudinal muscle preparations of guinea pig ileum.

Spontaneous tone of longitudinal muscle in guinea pig ileum was investigated in three types of preparations, intact segment preparation, segment preparation deprived of the mucosal layer and longitudinal strip preparation. Tone was defined as the sustained contraction that was lost by 10(-7) M atropine in the isotonically recorded manner. The magnitudes of tone were constant for at least 3 hr in the two types of segment preparations. Contractions in response to 10(-6) M acetylcholine, which were induced 9 times with an interval of 20 min between each induction, were almost identical throughout the period. In the longitudinal strip preparation, on the other hand, the tone gradually decayed and was eventually lost, while the amplitudes of acetylcholine-induced contractions were reciprocally increased. The tone in the intact segment preparation was reduced to 19% of the control by tetrodotoxin (3 x 10(-7) M), to 51% by indomethacin (3 x 10(-6) M) and to 26% by N6-cyclopentyladenosine (10(-7) M), but was not affected by AA-861 (3 x 10(-6) M) or CP-96,345 (3 x 10(-7) M). In the three types of preparations, the dose-response curves for acetylcholine were alike with similar EC50s. These results suggest that the tone of longitudinal muscle was mainly induced due to neural activity in the myenteric plexus of guinea pig ileum and that sensitivity to acetylcholine was not affected by the neural activity.

Acetylcholine↗