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PubMed1976

Biochemical aspects of experimental cardiac hypertrophy.

In experimental cardiac hypertrophy induced by aortic constriction of rats, the hypertrophy was established after 5-7 days. The basic biochemical changes for increasing tissue mass; increases in protein, nucleic acid, and polyamine synthesis started to occur between 2 and 8 hours followed by an increase in uridine nucleotide pools via predominance of "salvage" pathway. Although the precise coupling mechanism between mechanical stress and biochemical changes is still obscure, an interval between increased load and DNA transcription may be quite short. Some of the key enzymes regulating these processes showed a biphasic response the reason of which is not clear. The established hypertrophied heart muscle showed a decrease in velocity of isotonic shortening and an increase in resting tension. The former alteration is referred to a decrease in myosin ATPase activity and an disorder in excitation-contraction coupling mechanism, and the latter is supposed to be due to an increase in collagen in heart muscle.

Adenosine Triphosphatases↗
PubMed1978

Contractile properties of actomyosin from human blood platelets.

Actomyosin was purified from human blood platelets and used to form threads via extrusion. A sensitive tensiometer was employed to measure isometric tension and velocity of isotonic shortening of the threads in the presence of MgATP. Using fully phosphorylated myosin, we obtained values for maximum isometric tension (Po) and maximum velocity of contraction (V max) that were similar to those reported for threads composed of skeletal muscle actomyosin. Po was found to be directly proportional to the level of phosphorylation of the 20,000-dalton myosin light chain. We also studied the effect of phosphorylation on superprecipitation of platelet actomyosin. Fully phosphorylated myosin produced rapid clearing and superprecipitation, while myosin with a low level of bound phosphate underwent rapid clearing but did not superprecipitate. We have concluded from these results that: 1) the interaction between platelet actin and myosin produces tension and motion that is similar to that produced by skeletal muscle actin and myosin and 2) phosphorylation of the 20,000-dalton myosin light chain in important in controlling the production of force by platelet actin and myosin.

Actomyosin↗
PubMed1988

Pauses, steps, and the mechanism of contraction.

Despite widespread controversy still surrounding the phenomenon, stepwise shortening has now been confirmed by five independent methods in this laboratory, and by several other methods in different laboratories. In this paper we offer preliminary evidence obtained with the most recent method--measurement of 'isotonic muscle length transients'. We find that the muscle length inflections observed after quick release to an isotonic load correspond to pauses and steps at the sarcomere level. Thus, pauses and steps are reflected not only in sarcomere length and segment length signals, but in the muscle length signal as well. We review several of the more illuminating features of stepwise shortening, as well as new ultrastructural observations which, taken together, point to an hypothesis for the generation of steps. The steps may be generated by shortening of one or another of the sarcomere's filaments: connecting filaments in the unactivated myofibril and thick filaments in the activated myofibril. Supporting evidence is considered.

Animals↗
PubMed2001

Excitatory actions of experimental muscle pain on early and late components of human jaw stretch reflexes.

It has recently been shown that a slow stretch evokes a short-latency (probably monosynaptic) and a long-latency (polysynaptic) reflex response in human jaw-closing muscles. The effect of nociceptive muscle input on the fusimotor system has not been investigated in detail. In order to investigate the effect of sustained muscle pain on the jaw stretch reflex, two main experiments were performed. Stretch reflex responses were evoked in the masseter and temporalis muscles by slow stretches (1-mm displacement, 40-ms ramp time) before, during and 15 min after a period of experimentally induced muscle pain. In experiment I, a dose of 1.0 M hypertonic or 154 mM isotonic (control) saline was infused in random order into the left masseter for up to 15 min (n=12). The level of excitation of the left masseter at 15% maximal voluntary contraction was controlled by visual feedback of the surface EMG (sEMG). In experiment II, a dose of 1.0 M saline was infused into the left masseter but with feedback from the sEMG of the right masseter (n=12). In a control experiment, both sEMG and intramuscular EMG (imEMG) were recorded from the left and right masseters; the feedback was from imEMG of the left masseter (n=12). The early (onset: 9--10 ms) and late (duration from 25 to 40 ms) reflex components were recorded and analysed in all experiments. Infusion of 1.0 M saline caused moderate pain (mean score on a Visual Analogue Pain Scale: 4.9--5.0 cm). The peak-to-peak amplitude of the early reflex component in the painful masseter normalized to the pre-stimulus EMG activity was significantly higher during the pain than the pre- and post-infusion conditions in all experiments. The normalized area of the late reflex component in the painful masseter was significantly larger than in the pre-infusion condition in all experiments. Isotonic saline had no significant effect on the jaw stretch reflexes. These results indicate that experimental jaw-muscle pain in humans facilitates the early as well as the late component of the jaw stretch reflex response as revealed by both sEMG and imEMG. This effect appears to be independent of the level of excitation of the muscle and not related to volume effects of the injected saline. A change in the sensitivity of the fusimotor system during muscle pain is suggested as an explanation.

Adult↗
PubMedDate not supplied

Myocardial function in different models of cardiac hypertrophy. An attempt at correlating mechanical, biochemical, and morphological parameters.

Based on mechanical, biochemical and electron microscopic studies performed in the same stage of experimental cardiac hypertrophy, an attempt is made to define the significance of individual factors responsible for the alterations in myocardial function. Using swimming rats, it is demonstrated that a load-induced increase in cardiac mass is not necessarily connected with an impairment of contractile capability on a cellular level. Yet, also, the reduction of specific ATPase activity and unloaded shortening velocity in pressure-induced hypertrophy (goldblatt rats; aortic stenosis) seems to be the expression of adaptation rather than of cellular damage, at least in the earlier stages. Although there are distinct indications of alterations in Ca-dependent activation and deactivation, in the Goldblatt model electromechanical coupling does not seem to be the main cause of altered contraction parameters. The correlation between specific ATPase activity of actomyosin and unloaded shortening velocity as well as the persistance of decrease in shortening velocity, also under optimal electromechanical coupling conditions, point to an inner relationship between the two values. A discrepancy between unloaded shortening velocity on the one hand and developed tension on the other is mainly due to an increased content of contractile structures. In later stages, an increased connective tissue content influences both isometric and isotonic parameters.

Actomyosin↗
PubMed1992

The location of the receptors involved in the human diuretic response to drinking an isotonic electrolyte solution.

1. This study aimed to shed light on the receptors involved in the diuretic response to drinking isotonic fluids in man by employing a polyethylene glycol-based bowel lavage solution (Golytely) which is reported to cause no net movement of fluid across the gut. 2. Drinking Golytely resulted in a transient hypotonic diuresis. Mean urine flow rose from control values of 0.9 ml min-1 to 10.1 ml min-1 70 min after the start of drinking. The increase in urine output was accompanied by a fall in urine osmolality from control values of 879 mosM kg-1 to 105 mosM kg-1. The diuresis is similar to that produced by ingestion of an equal volume of an absorbable electrolyte-based solution (Tyrode). 3. Neither solution produced changes in plasma osmolality or electrolytes, but Golytely provoked a 6.8% contraction of plasma volume, whereas drinking Tyrode resulted in plasma expansion. Copious diarrhoea was experienced by all subjects who drank Golytely solution and by none on drinking Tyrode solution. 4. The infusion of Golytely into the stomach resulted in a hypotonic diuresis similar in magnitude to that elicited by drinking. Drinking with simultaneous aspiration of gastric contents ('sham-drinking') did not produce a significant diuresis. 5. Plasma arginine vasopressin (AVP) levels did not fall following the drinking of Golytely. The assay used was sufficiently sensitive to measure changes of 0.6 pg AVP (ml plasma)-1. 6. The findings show that signals from the oropharynx do not mediate the diuretic response to drinking Golytely in man and that a mechanism other than inhibition of AVP release appears to be involved. The receptors mediating this response may lie in the stomach and/or small bowel since Golytely is not absorbed, as evidenced by the contraction of plasma volume and diarrhoea.

Adult↗
PubMed1963

Total energy production and phosphocreatine hydrolysis in the isotonic twitch.

Using frog's sartorius muscles we have found no correlation between phosphocreatine hydrolysis and shortening under conditions (iodoacetate poisoning and anoxia) where this reaction was the only expected source of energy. Phosphocreatine hydrolysis did, however, show a constant term corresponding to the activation heat of A.V. Hill, and a linear term with work. It was concluded that shortening heat comes from some other chemical reaction, or else Hill's equation (E = A + W + ax) fails to describe correctly the energy output in a complete cycle of contraction and relaxation. To decide between these possibilities direct measurements of heat and work during a complete cycle were made. Also, experiments were performed in which heat, work, and phosphocreatine breakdown were measured simultaneously on the same muscles. The total energy output in a complete twitch could be most simply represented by a fixed "activation" heat, plus the work. There was no term corresponding to the shortening heat. Hill's equation must, therefore, be held as invalid for the complete isotonic twitch. A value of 9.8 +/- 0.5 (sE) kcal/mole was obtained for the in vivo heat of hydrolysis of phosphocreatine. This quantity showed no significant dependence on load, and it is in good agreement with the value obtained from thermochemical data. It is concluded that phosphocreatine hydrolysis and its associated buffer reactions can account quantitatively for the total energy output of isometric and isotonic twitches.

Animals↗
PubMed1984

From activity to rest: gating of excitatory autogenetic afferences from the relaxing muscle in man.

The changes in reflex excitability of the motoneurones to the soleus (Sol) muscle occurring during and after voluntary releases of various duration from a constant plantar-torque level in isometric or isotonic conditions have been investigated in normal humans by means of the H-reflex and T-response. The amplitude of both reflexes during the release phase attains values lower than control (obtained in resting conditions) even in the presence of force and EMG activity; the maximal inhibition is reached at the end of the release; the reflexes recover gradually to control values over several seconds. The more abrupt is the release, the more inhibited is the reflex and the shorter is the time to recovery and vv. These results apply both in isometric and isotonic conditions. Activation of the antagonist muscles, sometimes occurring at the end of the fastest release, does not contribute to the H-reflex inhibition. Tonic isometric contractions and relative releases have also been evoked by the tonic vibration reflex (TVR). The H-reflex during the TVR-induced contractions were lower than control values, at variance with those obtained during the voluntary contractions, but their amplitudes during the releases had similar values and time-courses in both conditions, pointing to a common involved inhibitory mechanism. Any voluntary ballistic or ramp contraction taking place after a preceding release, in the period in which the H-reflexes were still inhibited, was not apparently influenced, despite the fact that H-reflexes evoked during the release-conditioned ramp contractions were significantly lower than when evoked during control ramps of similar characteristics. The results are discussed in terms of a premotoneuronal, possibly presynaptic, inhibitory mechanism.

Adult↗
PubMed1983

Technique for stabilizing the striation pattern in maximally calcium-activated skinned rabbit psoas fibers.

A procedure was developed for stabilizing the striation pattern of fully activated skinned rabbit psoas fibers. Inhomogeneities of the striation pattern that develop during the rise in tension and also during isometric steady state are completely reversible by this procedure. The striation pattern can be stabilized for approximately 2 h. During this period isometric tension and speed of isotonic shortening decrease less than 10-20% of their initial values.

Animals↗
PubMed2000

Influence of 5-hydroxytryptamine and the effect of a new serotonin receptor antagonist (sarpogrelate) on detrusor smooth muscle of streptozotocin-induced diabetes mellitus in the rat.

BACKGROUND: We evaluated the changes in the response of detrusor muscle to 5-hydroxytryptamine (5-HT; serotonin) and its receptor mechanisms in pathologic bladder of diabetes mellitus rats. METHODS: Eight-week-old male Wistar rats were given an intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in order to induce diabetes mellitus (4 weeks' duration). The bladder strips (10 x 2 mm) were subjected to a tension of 1.0 g in organ baths for the measurements of isotonic contractile responses to 5-HT or relaxation responses to 5-HT antagonists. RESULTS: Bladder strips from STZ-diabetic rats responded to 5-HT with greater contractions than did those of control rats, given vehicle alone. However, bladder strip weights gradually increased in the STZ-diabetic rats as compared with control rats and when the contractile response to 5-HT was expressed as a percentage of the response to 10(-1) mol/L KCl there was no statistically significant difference between the groups. In both control and diabetic rats, the 5-HT3 selective antagonist did not markedly inhibit the contractile response to 5-HT. In contrast, the 5-HT2A selective antagonist inhibited the contractile response to 5-HT in a dose-dependent manner. CONCLUSIONS: These results suggest that the increased contractile response to 5-HT in diabetic rats' bladder is related to smooth muscle hypertrophy and/or hyperplasia and indicate that this effect is mediated by activation of 5-HT2A receptors.

Animals↗
PubMed2001

Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses.

OBJECTIVE: The seeds of Nigella sativa locally known as "Kalonji" has been used in traditional medicine for the treatment of a variety of diseases including diarrhoea and asthma. The crude extract of N. sativa seeds (Ns.Cr) was studied in vitro for its possible spasmolytic and bronchodilator activities to rationalize the folkloric uses. METHODS: Isolated rabbit jejunum and guinea-pig tracheal preparations were set up in Tyrode's and Kreb's solutions respectively and aerated with 5% CO2 in oxygen. Isotonic and isometric responses were measured on Bioscience oscillograph and Grass polygraph respectively. RESULTS: The Ns.Cr caused a dose-dependent (0.1-3.0 mg/ml) relaxation of spontaneous contractions in rabbit jejunum. Ns.Cr also inhibited K(+)-induced contractions in a similar dose range, suggestive of calcium channel blockade (CCB). This effect was confirmed when pretreatment of the tissue with Ns.Cr, produced a dose-dependent shift in the Ca++ dose-response curves to the right similar to that of verapamil, a standard calcium channel blocker. In guinea-pig trachea, it caused relaxation of carbachol-, histamine- or K(+)-induced contractions indicating CCB. Activity-directed fractionation revealed that the CCB activity is concentrated in the petroleum ether fraction, which was found to be approximately 10 times more potent than the crude extract both in jejunum and tracheal preparations. CONCLUSION: These data indicate that the crude extract of Nigella sativa seeds exhibits spasmolytic and bronchodilator activities mediated possibly through calcium channel blockade and this activity is concentrated in the organic fraction. Its usefulness for diarrhoea and asthma in traditional medicine, appears thus to be based on a sound mechanistic background.

Animals↗
PubMed1981

Pulmonary edema following ritodrine-saline infusion in premature labor.

Twenty-three patients with premature uterine contractions occurring between the 27th and 35th weeks of pregnancy were treated in a prospective and randomized study with intravenous ritodrine in a 0.1 wt/vol% solution of isotonic saline (N = 12) or isotonic glucose (N = 11). The aim of the study was to record the effects of these agents on the water-salt metabolism. In both the saline and the glucose groups there was a statistically significant fall in hemoglobin, hematocrit, and serum albumin (P less than .001). This fall correlated significantly with the dose of ritodrine (P less than .001). Serum renin and aldosterone levels revealed a statistically significant increase (P less than .0005). Seven of 12 patients in the saline group, but none in the glucose group, developed pulmonary congestion requiring treatment. The combination of ritodrine and saline should be used very cautiously, and the authors recommend accurate monitoring of the fluid balance during ritodrine treatment.

Aldosterone↗
PubMed1995

GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function.

Gamma-aminobutyric acid (GABA) antagonist (bicuculline methiodide, BIC; picrotoxin, PIC) or agonist (muscimol, MUS) microinjections were made into the dorsal motor nucleus of the vagus nerve (DMV), and effects on lower esophageal sphincter pressure (LESP), gastric motility, and gastric acid secretion were determined in chloralose-anesthetized cats. Right or left DMV sites were microinjected with BIC, PIC, MUS, or isotonic tonic saline (140 nl) through a glass micropipette having a tip diameter of 15-21 microns. Esophageal body, LESP, and gastric fundic pressures were measured manometrically. Circular smooth muscle contractions of the antrum and pylorus were recorded with strain-gauge force transducers. Gastric acid secretion was measured every 15 min through a gastric cannula and titrated to pH 7.0. DMV microinjection sites were verified histologically. Direct BIC microinjections (0.275 or 0.550 nmol) into the DMV primarily produced a decrease in LESP (71% of all sites tested), with mean LESP changing from 23.2 +/- 1.7 mmHg to 3.7 +/- 0.7 mmHg (p < 0.01). Tonic LESP increases and phasic LESP contractile activity occurred less frequently. BIC-induced LESP responses were abolished by vagotomy or by microinjections of MUS (0.5 to 10 nmol) into the DMV. Direct PIC microinjection (0.232 nmol) into the DMV produced a pattern of responses similar to those observed with BIC (which were also abolished by vagotomy or by MUS microinjections into the DMV). The antrum and pylorus were also responsive to DMV microinjections of both GABA antagonists. Microinjections of BIC or PIC into the DMV produced increases in gastric circular muscle activity that occurred less frequently than LESP effects, but also were eliminated by vagotomy. The high (0.550 nmol) dose of BIC increased gastric motility significantly more often than the low dose of BIC (p < 0.05). In addition, BIC (0.550 nmol) microinjections into the DMV increased gastric secretory volume (from 0.6 +/- 0.2 to 6.0 +/- 2.5 ml/15 min; p < 0.01) and total titratible acid (from 34.4 +/- 8.9 to 86.0 +/- 19.1 mEq/15 min; p < 0.01), and decreased gastric pH (from 4.63 +/- 0.44 to 3.50 +/- 0.49; p < 0.05). Vagotomy also eliminated the gastric secretory effects of DMV BIC. Direct microinjections of MUS into the DMV also blocked BIC- or PIC-induced changes in gastric motility and/or gastric acid secretion. Isotonic saline microinjected into the DMV did not increase basal or decrease stimulated gastric esophageal motility or gastric secretion. These data indicate that LESP, gastric motility, and gastric secretion are influenced by a tonic DMV inhibition mediated by GABAA receptor stimulation of the DMV. Because disinhibition of these receptors clearly activates the upper gut, future work should focus on identifying the nuclei providing this synaptic input to the DMV that might be involved in the functional regulation of upper gut motor and secretory function.

Animals↗
PubMed1976

[Effect of anoxia on energy supply and isotonic work performance in the myocardium of the frog].

To investigate correlations between energy supply and mechanical work in the frog's myocardium in true anoxia, the stroke volume, systolic and diastolic volumes and the parameters of velocity of contraction and relaxation of frog hearts were compared to the levels of high energy phosphates and the delivery of lactate. During perfusion with N2 saturated Ringer solution, stroke volume, systolic contractility and diastolic relaxation decrease till a contracture. High preload produces a dilatation growing up to the contracture after retarded and weakened relaxation. The ATP-content decreases during the first quarter of the experiment to 60%. CP decreases continuously to 15%, ADP and AMP remain constant. There is a production of lactate increasing considerably with the onset of contracture. The measured glycolysis is not sufficient for production of mechanical work. The effect of anoxia on the action potential and the reduction of the sequestration of Ca++ and of the break of actomyosin bridges following the decrease of ATP are considered as causing the series of the mechanical events.

Adenosine Diphosphate↗
PubMed1997

The signalling pathway which causes contraction via P2-purinoceptors in rat urinary bladder smooth muscle.

1. The signalling pathway which causes contractions to adenosine 5'-O-2-thiodiphosphate (ADPbetaS) and alpha,beta-methylene adenosine 5'-diphosphate (alpha,beta-Me ADP) was investigated in rat urinary bladder smooth muscle by measuring isotonic tension. 2. The responses to 10 microM alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-Me ATP) in 0 and 3.6 mM Ca2+ were 5.9+/-1.3 (n=10) and 122.2+/-6.4 (n=8) % respectively of those obtained in 1.8 mM Ca2+, whereas those to 100 microM ADPbetaS were 34.6+/-3.3 (n=8) and 96.8+/-7.2 (n = 8) %, in 0 and 3.6 mM Ca2+, respectively. In both experimental conditions, the responses to the two agonists expressed as % of the control responses were significantly different (P<0.01). 3. Indomethacin at high concentrations (>1 microM) decreased the responses to alpha,beta-Me ATP (10 microM), ADPbetaS (100 microM) and alpha,beta-Me ADP (100 microM). However, no significant difference was obtained between the responses to all the agonists at 30 microM indomethacin. 4. 2-Nitro-4-carboxphenyl n,n-diphenylcarbamate (NCDC) at concentrations between 1 microM and 100 microM concentration-dependently decreased the responses to ADPbetaS (100 microM) and alpha,beta-Me ADP (100 microM) and almost completely inhibited them at 100 microM. Although the responses to alpha,beta-Me ATP (10 microM) were also inhibited by the drug, at 50 and 100 microM NCDC the responses to alpha,beta-Me ATP were significantly larger than those to ADPbetaS and alpha,beta-Me ADP (P<0.01). 5.NCDC 100 microM significantly inhibited the KCl-induced contraction to 65.9+/-4.9% (n=6) of the control (P<0.01). 6. It is suggested that the contraction via ADPbetaS-sensitive receptors in the rat urinary bladder smooth muscle mainly depends on Ca2+ ions liberated from intracellular Ca2+ stores, though the contribution of Ca2+ ions from the extracellular space cannot be neglected. The release of Ca2+ ions from stores is mainly mediated by the production of inositol trisphosphate (IP3) via the activation of phospholipase C.

Adenosine Diphosphate↗
PubMed1982

Mechanics of myocardial relaxation: application of a model to isometric and isotonic relaxation of rat myocardium.

Using a simple model for cardiac muscle relaxation which takes into account muscle length, activation, elasticity and a rate constant for the decay of activation, we are able to use easily measured mechanical parameters to assess the state of the cardiac relaxing system. In isolated trabeculae carneae from the left ventricle of the rat, performing physiologically sequenced contractions, observations have been made (1) at varying preloads and afterloads, (2) with changes in temperature from 23 degrees to 33 degrees C, (3) with changes in bath Ca2+ concentration and (4) with the addition of isoproterenol. During isometric relaxation, the slope (SIM) of the curve relating maximum rate of decline of force (-dF/dtmax) to end-systolic muscle length is load-independent and sensitive to interventions which directly affect the cardiac relaxing system (e.g., temperature, isoproterenol); it is only slightly sensitive to bath calcium concentration. During isotonic relaxation, the maximum velocity of lengthening (+dL/dtmax) is in negative linear proportion to muscle shortening at a given preload, the slope (SIT) of the curve relating +dL/dtmax to end-systolic length is sensitive to the interventions which directly affect the cardiac relaxing system but insensitive to calcium-mediated inotropic interventions. The model provides a theoretical basis for the use of SIM and SIT as measures of the relaxation process.

Animals↗