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Recruitment of single human low-threshold motor units with increasing loads at different muscle lengths.

We investigated the recruitment behaviour of low threshold motor units in flexor digitorum superficialis by altering two biomechanical constraints: the load against which the muscle worked and the initial muscle length. The load was increased using isotonic (low load), loaded dynamic (intermediate load) and isometric (high load) contractions in two studies. The initial muscle position reflected resting muscle length in series A, and a longer length with digit III fully extended in series B. Intramuscular EMG was recorded from 48 single motor units in 10 experiments on five healthy subjects, 21 units in series A and 27 in series B, while subjects performed ramp up, hold and ramp down contractions. Increasing the load on the muscle decreased the force, displacement and firing rate of single motor units at recruitment at shorter muscle lengths (P<0.001, dependent t-test). At longer muscle lengths this recruitment pattern was observed between loaded dynamic and isotonic contractions, but not between isometric and loaded dynamic contractions. Thus, the recruitment properties of single motor units in human flexor digitorum superficialis are sensitive to changes in both imposed external loads and the initial length of the muscle.

Action Potentials↗

Selective recruitment of high-threshold human motor units during voluntary isotonic lengthening of active muscles.

1. We have investigated the possibility that voluntary muscle lengthening contractions can be performed by selective recruitment of fast-twitch motor units, accompanied by derecruitment of slow-twitch motor units. 2. The behaviour of motor units in soleus, gastrocnemius lateralis and gastrocnemius medialis muscles was studied during (a) controlled isotonic plantar flexion against a constant load (shortening contraction, S), maintained plantar flexion, or dorsal flexion resisting the load and gradually yielding to it (lengthening contraction, L), (b) isometric increasing or decreasing plantar torque accomplished by graded contraction or relaxation of the triceps surae muscles, (c) isometric or isotonic ballistic contractions, and (d) periodic, quasi-sinusoidal isotonic contractions at different velocities. The above tasks were performed under visual control of foot position, without activation of antagonist muscles. The motor units discharging during foot rotation were grouped on the basis of the phase(s) during which they were active as S, S + L and L. The units were also characterized according to both the level of isometric ramp plantar torque at which they were first recruited and the amplitude of their action potential. 3. S units were never active during dorsal flexion; some of them were active during the sustained contraction between plantar and dorsal flexion. Most S + L units were active also during the maintenance phase and were slowly derecruited during lengthening; their behaviour during foot rotations was similar to that during isometric contractions or relaxations. L units were never active during either plantar or maintained flexion, but discharged during lengthening contraction in a given range of rotation velocities; the velocity of lengthening consistently influenced the firing frequency of these units. Such dependence on velocity was not observed in S + L units. 4. A correlation was found between the amplitude of the action potential and the threshold torque of recruitment among all the units. In addition, the amplitudes of both the action potential and the threshold torque were higher in the case of L units than in the case of S and S + L units. Most L units could be voluntarily recruited only in the case of ballistic isometric or isotonic contraction. 5. Occasionally, L units were directly activated by electrical stimulation of motor fibres and their conduction velocity was in the higher range for alpha-axons. In contrast, nerve stimulation could induce a reflex activation of S and S + L units.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Studies on the effects of nitrendipine on oxytocin, angiotensin II and ergometrine-induced contraction of pregnant human myometrium in vitro.

The effects of nitrendipine, a Calcium channel antagonist, on stimulated contractions of 72 tissue strips of pregnant human myometrium was studied. The agonists used were oxytocin, angiotensin II (AII) and ergometrine maleate. The concentration: response curves for the contractile effects on these agonists on the myometrial tissue strips were initially established in three separate but identical experiments (n = 24 in each group) over a predetermined optimal concentration range of each of the agonists. Contractions were recorded isotonically against a fixed tension of 500mg using microtorque technique. The curves were then re-established, for each agonist, in the absence and in the presence of 10(-9)M nitrendipine. The agonists consistently contracted the myometrial tissues in a dose-dependent manner during the establishment of the initial curves. The overall initial EC50 for the oxytocin treatment group was 6.4 x 10(-10)M, while the corresponding EC50s for the AII, and ergometrine treatment groups were 5.9 x 10(-11) and 4.0 x 10(-8)M respectively. Nitrendipine significantly blunted the myometrial tissue response to oxytocin. The EC50 of the oxytocin control group was significantly different from similar group treated with nitrendipine. (9.0 x 10(-10)M for the control, as compared with 8.3 x 10(-7)M for the nitrendipine treatment group p less than or equal to 0.05). Nitrendipine did not significantly influence the myometrial tissue response to AII or ergometrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Cyclic production of tension force in the plasmodial strand of Physarum polycephalum and its relation to microfilament morphology.

Cyclic contraction and relaxation of plasmodial strands of Physarum polycephalum were measured under both isotonic and isometric conditions, and their relation to changes in microfilament (MF) morphology was investigated. The contraction-relaxation rhythm of a strand segment was insignificant and irregular immediately after isolation from the mother plasmodium. It became regular half an hour later when local minute rhythms were synchronized spontaneously. If a strand kept under isotonic conditions was loaded with a heavier weight or a strand kept under isometric conditions was stretched a few times, the amplitude of each contraction wave was enhanced. After a strand had been thus conditioned, it was fixed at a selected phase of the contraction-relaxation cycle under both isotonic and isometric conditions. The state of MFs changed strikingly according to the phase of the contraction cycle. In the shortening phase of the strand under isotonic contractions, MFs with a diameter of 6--7 nm were arranged parallel to each other to form large compact bundles in which adjacent filaments were bridged with cross linkages. Among these MFs, thicker filaments were sporadically scattered. At about the phase of minimal strand length, most of the MFs became kinky and formed networks. In the elongating phase, new loose bundles of MFs developed from the network. These loose bundles became compact again when the strand reached its maximal elongation phase. In the isometric contraction, MFs in the increasing tension phase were nearly the same as those in the shortening phase in isotonic contraction. Around the maximal tension phase, dense areas of MFs appeared along the bundles in place of the network formed in the isotonic contraction phase. These areas were closely packed, with MFs arranged parallel to each other. In the decreasing and minimal tension phases in isometric contraction, MFs were arranged similarly to those in the elongating and maximally elongated phases, respectively, in isotonic contraction. Alternation between the straight bundle and fine network configuration of the MFs observed in isotonic contraction was inconspicuous in isometric contraction. This was probably due to spatial restriction of shortening under isometric contraction. The results are interpreted in terms of cyclic changes of the aggregation pattern of the MFs in the form of F-actin, as opposed to the possibility that the contraction-relaxation cycles depend on cyclic G-F transformation of actin.

Biomechanical Phenomena↗

Further studies on the effects of ketotifen on guinea pig ileum.

Ketotifen (Ke) at the concentration of 10(-5) M or greater significantly inhibits guinea pig ileum contractions induced by cumulative dose response curves to Pg alpha F2 or BaCl2. This inhibitory effect of Ke is also observable against ileal contractions induced by isotonic and hypertonic solutions with high K+ and by electrical stimulation. In contrast to the long term antihistaminic effect of DSCG and Ke, the latter drug exhibits a shorter inhibitory effect when Ach and electrical stimulation are used to induce ileal contractions shortly after Ke is removed by washing from the organ bath. This nonspecific protective effect of Ke on smooth muscle against various spasmogens resembles the one reported recently by us for DSCG and might be relevant to the antiallergic and antiasthmatic properties of both drugs.

Acetylcholine↗

Effects of magnesium ion and temperature on the phasic and tonic contractions of the potassium contracture in the pregnant rat myometrium.

Effects of Mg ion, low temperature and 2,4-dinitrophenol on the Kcontracture were investigated in pregnant rat uteri. At 36-38degrees C, the addition of Mg ions increased the amplitude of tonic contraction when the isotonic K media contained 2.2 mM Ca (inhibitory effect). When the muscle strip was loaded with Mg ion by exposing it previously to a Locke-Ringer solution containing 1as nearly abolished but the inhibitory effect persisted. The amplitude of the tonic contraction was reduced, and the potentiating effect of the Mg ion was depressed at lower temperatures. The inhibitory effect persisted at low temperatures. The time course of relaxation of the phasic contraction consisted of two exponentials, the initial one fast and succeeding one slow. The effect of Mg on the relaxation during the initial phase was variable, butthe succeeding one always became slower when Mg ions were added. The initial phase of the relaxation became slower at lower temperatures. However, the succeding phase became faster. The above experimental results were interpreted to suggest that the sites of Mg action were two, one being at the outer surface of the membrane competing for occupation with Ca ions, and the other within or at the inner surface of the membrane regulating the amount of bound Ca which is in turn utilized to evoke contraction. The latter is probably mediated by metabolic processes.

Animals↗

A new tension-adjustment technique for sling operation: an animal model.

OBJECTIVE: To investigate the effectiveness of a new tension-adjustment technique for postoperative voiding difficulties encountered after sling operations. METHOD: To test our new method, urethral obstruction was developed in 5 female dogs by modifying the sling operation by exerting more tension on a specially prepared polypropylene strip in which a gap had been developed. After filling the bladder with isotonic solution, detrusor contractions were induced by pelvic nerve stimulations, and urodynamic studies were performed to document the urethral obstruction. In each case Foley catheters were inserted into the bladder and left in place until the time of tension adjustment. Tension adjustment was performed in the 1st, 2nd, 3rd, 4th and 5th weeks postoperatively for dogs 1, 2, 3, 4, and 5, respectively. RESULTS: On the day of tension adjustment, after filling the bladder with isotonic solution and removing the Foley catheter, none of the dogs, except dog 3, was able to produce a free flow of urine either spontaneously or provoked by detrusor contractions. The release of the prolene sutures was readily achieved in all cases except dog 5. In this case, sling takedown was achieved after surgical exploration in which the sling location was confirmed by following the prolene sutures and Hegar's dilator. After identifying the sling, the gap was opened by cutting the prolene sutures, instead of a sling incision. Release of the prolene sutures resulted in a distinct drop in the urethra with decreased resistance of Hegar's dilator. The improvement in voiding was confirmed by postoperative urodynamic studies and was immediate in all cases. CONCLUSION: Our new technique for postoperative voiding difficulties encountered after sling operation is simple, effective and avoids re-operation in the early postoperative period.

Animals↗

Hydrogen peroxide decreases Ca(2+) sensitivity in airway smooth muscle by inhibiting rMLC phosphorylation.

The purpose of this study was to determine the mechanism by which hydrogen peroxide (H(2)O(2)), an important inflammatory mediator, relaxes canine tracheal smooth muscle (CTSM). H(2)O(2) caused concentration-dependent relaxations of CTSM strips contracted with ACh or isotonic KCl [EC(50) of 0.24 +/- 0.04 (SE) and 0.23 +/- 0.04 mM, respectively]. Indomethacin (10 microM) decreased the sensitivity of both KCl- and ACh-contracted strips to H(2)O(2). H(2)O(2) increased intracellular cAMP levels, an increase that was abolished by indomethacin. H(2)O(2) did not affect intracellular cGMP levels. In strips treated with indomethacin and contracted with ACh or isotonic KCl, H(2)O(2)-evoked relaxations were accompanied by increases in intracellular Ca(2+) concentration and decreases in regulatory myosin light chain phosphorylation. We conclude that H(2)O(2) decreases Ca(2+) sensitivity in CTSM by decreasing regulatory myosin light chain phosphorylation through inhibition of myosin light chain kinase and/or activation of smooth muscle protein phosphatases.

Acetylcholine↗

Temperature dependence of mammalian muscle contractions and ATPase activities.

Isolated rat and mouse extensor digitorum longus (EDL) and soleus muscles were studied under isometric and isotonic conditions at temperatures from approximately 8 degrees -38 degrees C. The rate constant for the exponential rise of tension during an isometric tetanus had a Q10 of approximately 2.5 for all muscles (corresponding to an enthalpy of activation, delta H = 66 kJ/mol, if the rate was determined by a single chemical reaction). The half-contraction time, contraction time, and maximum rate of rise for tension in an isometric twitch and the maximum shortening velocity in an isotonic contraction all had a similar temperature dependence (i.e., delta H approximately 66 kJ/mol). The Mg++ ATPase rates of myofibrils prepared from rat EDL and soleus muscles had a steeper temperature dependence (delta H = 130 kJ/mol), but absolute rates at 20 degrees C were lower than the rate of rise of tension. This suggests that the Mg++ ATPase cycle rate is not limiting for force generation. A substantial fraction of cross-bridges may exist in a resting state that converts to the force-producing state at a rate faster than required to complete the cycle and repopulate the resting state. The temperature dependence for the rate constant of the exponential decay of tension during an isometric twitch or short tetanus (and the half-fall time of a twitch) had a break point at approximately 20 degrees C, with apparent enthalpy values of delta H = 117 kJ/mol below 20 degrees C and delta H = 70 kJ/mol above 20 degrees C. The break point and the values of delta H at high and low temperatures agree closely with published values for the delta H of the sarcoplasmic reticulum (SR) Ca++ ATPase. Thus, the temperature dependence for the relaxation rate of a twitch or a short tetanus is consistent with that for the reabsorption rate of Ca++ into the SR.

Adenosine Triphosphatases↗

Rho/Rho-dependent kinase affects locomotion and actin-myosin II activity of Amoeba proteus.

The highly motile free-living unicellular organism Amoeba proteus has been widely used as a model to study cell motility. However, the molecular mechanisms underlying its unique locomotion are still scarcely known. Recently, we have shown that blocking the amoebae's endogenous Rac- and Rho-like proteins led to distinct and irreversible changes in the appearance of these large migrating cells as well as to a significant inhibition of their locomotion. In order to elucidate the mechanism of the Rho pathway, we tested the effects of blocking the endogenous Rho-dependent kinase (ROCK) by anti-ROCK antibodies and Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride, a specific inhibitor of ROCK, on migrating amoebae and the effect of the Rho and ROCK inhibition on the actin-activated Mg-ATPase of the cytosolic fraction of the amoebae. Amoebae microinjected with anti-ROCK inhibitors remained contracted and strongly attached to the glass surface and exhibited an atypical locomotion. Despite protruding many pseudopodia that were advancing in various directions, the amoebae could not effectively move. Immunofluorescence studies showed that ROCK-like protein was dispersed throughout the cytoplasm and was also found in the regions of actin-myosin II interaction during both isotonic and isometric contraction. The Mg-ATPase activity was about two- to threefold enhanced, indicating that blocking the Rho/Rho-dependent kinase activated myosin. It is possible then that in contrast to the vertebrate cells, the inactivation of Rho/Rho-dependent kinase in amoebae leads to the activation of myosin II and to the observed hypercontracted cells which cannot exert effective locomotion.

Acanthamoeba↗

Free radicals in tetanic activity of isolated skeletal muscle.

1. The concentration of the free radicals in muscle tissue mitochondria changes with the phase of muscle contraction. 2. Potassium cyanide (KCN) influences the shape of the isotonic tetani mechanograms; the contraction is still strong and qualitatively comparable in amplitude to untreated controls. 3. On the other hand, the correlation between the free radical concentration and muscle contraction is lost. 4. The free radical concentration in isolated mitochondria is influenced by KCN and potassium ferricyanide. 5. The free radical concentration changes due to the electron flow in the respiratory chain. 6. Inhibition of the respiratory phosphorylation by KCN could affect the free radical level.

Animals↗

Sense and nonsense about the Fenn effect.

One of the most influential papers in muscle physiology was published by W. O. Fenn (J. Physiol. London 58: 175-203) in 1923. Fenn determined the quantitative relationship between muscle energy liberation and work performance. Despite the importance of this work, the implications of Fenn's observations are sometimes misunderstood. In this review article, Fenn's experiments are reexamined and the Fenn effect delineated in light of the viscoelastic model of muscle contraction prevalent in the 1920's. The generality of Fenn's results and conclusions are considered in view of more recent results from skeletal and cardiac muscle. Factors responsible for the considerable deviation from Fenn's original results are discussed. Much of the confusion surrounding the generality of Fenn's observations seems to be attributable to the problem of determining an energetic base line for comparing isotonic and isometric contractions. Mommaerts (Physiol. Rev. 49: 427-508, 1969) has suggested the use of an equivalent force base line, which appears to be useful and unifying concept.

Animals↗

No evidence for a role of muscarinic M2 receptors in functional antagonism in bovine trachea.

1. The functional antagonism between methacholine- or histamine-induced contraction and beta-adrenoceptor-mediated relaxation was evaluated in bovine tracheal smooth muscle in vitro. In addition, the putative contribution of muscarinic M2 receptors mediating inhibition of beta-adrenoceptor-induced biochemical responses to this functional antagonism was investigated with the selective muscarinic antagonists, pirenzepine (M1 over M2), AF-DX 116 and gallamine (M2 over M3), and hexahydrosiladiphenidol (M3 over M2). 2. By use of isotonic tension measurement, contractions were induced with various concentrations of methacholine or histamine, and isoprenaline concentration-relaxation curves were obtained in the absence or presence of the muscarinic antagonists. Antagonist concentrations were chosen so as to produce selective blockade of M2 receptors (AF-DX 116 0.1 microM, gallamine 30 microM), or half-maximal blockade of M3 receptors (pirenzepine 0.1 microM, AF-DX 116 0.5 microM, hexahydrosiladiphenidol 0.03 microM). Since these latter antagonist concentrations mimicked KB values towards bovine tracheal smooth muscle M3 receptors, antagonist-induced decreases in contractile tone were compensated for by doubling the agonist concentration. 3. It was found that isoprenaline-induced relaxation of bovine tracheal smooth muscle preparations was dependent on the nature and the concentration of the contractile agonist used. Thus, isoprenaline pD2 (-log EC50) values were decreased 3.7 log units as a result of increasing cholinergic tone from 22 to 106%, and 2.4 log units by increasing histamine tone over a similar range. Furthermore, maximal relaxability of cholinergic tone decreased gradually from 100% at low to only 1.3% at supramaximal contraction levels, whereas with histamine almost complete relaxation was maintained at all concentrations applied. As a result, isoprenaline relaxation was clearly hampered with methacholine compared to histamine at equal levels of contractile tone.4. In the presence of gallamine, isoprenaline relaxation was facilitated for most concentrations of methacholine, and for all concentrations of histamine. These changes could be explained by the decreased contraction levels for both contractile agonists in the presence of gallamine.5. Isoprenaline-induced relaxation of cholinergic contraction was also facilitated by AF-DX 116 as well as by pirenzepine and hexahydrosiladiphenidol, and these (small) changes were again related to the(small) decreases in cholinergic contraction levels that were present in these experiments despite the additional administration of the agonist to readjust contractile tone. Similarly, changes in isoprenaline relaxation of histamine-induced tone could be explained by different contraction levels.6. These results can be explained by the sole involvement of muscarinic M3 receptors, and provide no evidence for a role of muscarinic M2 receptors in functional antagonism in bovine trachea. Furthermore,they stress the importance of taking into account non-cholinergic controls as well as contraction levels in these experiments.

Animals↗

Reflex activity and muscle tone during elbow movements in patients with spastic paresis.

Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis. During sinusoidal (0.3-Hz) isometric or isotonic elbow tracking, with a control either of joint position or of torque, randomly timed displacements were induced (at one of three velocities) stretching either the activated flexor or the extensor muscles. On the spastic side, exaggerated short-latency reflexes were apparent, but in contrast, the amplitude of long-latency electromyography (EMG) responses was reduced. The latter responses were differentially modulated on the unaffected side, predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque, while the mode of muscle contraction (isometric or isotonic) had little influence on this behavior. This difference in reflex modulation was lost on the spastic side. The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements. The ratio of torque to EMG activity during displacements was higher for both background and reflex-induced EMG on the spastic limb than on the unaffected side. This effect was more pronounced for the flexor than for the extensor muscles. Consequently, the development of spastic muscle hypertonia cannot be attributed to an increase in EMG activity. It is suggested that secondary to a supraspinal lesion, mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched.

Adolescent↗

The role of frequency in the effects of long-term intermittent stimulation of denervated slow-twitch muscle in the rat.

1. Rat soleus muscle was denervated by sciatic transection and electrically stimulated for periods of between 3 and 9 weeks with intermittent 1 s bursts of pulses. Most of the bursts were either repeated every 90 s and pulses within them had frequencies between 10 and 100 Hz, or had a frequency of 50 Hz and were repeated at intervals between 60 and 600 s. Comparisons were made with continuous stimulation at 10 Hz. 2. At the end of the period of stimulation, isometric twitches and tetani were measured and, in a proportion, also isotonic shortening velocity. 3. Isometric twitch duration (contraction and relaxation) decreased with time of stimulation. Very similar effects were seen in all animals in which intermittent stimulation had been used. There was a significant relationship between the change in twitch duration and the frequency used within the bursts of chronic stimulation, with slightly larger effects at frequencies of 40 and 60 Hz. The lowest burst repetition rate produced the largest effects. 4. It was confirmed that similar changes were found in denervated muscles that were not stimulated, although these changes were smaller and developed more slowly. 5. The extreme loss of tetanic tension induced in the muscle by denervation was reduced by chronic stimulation, with no significant difference between different regimes, although there were small differences which showed the same patterns of effectiveness described for twitch durations. 6. Continuous stimulation at 10 Hz maintained the twitch contraction and relaxation phases at the values found 3 weeks after denervation, that is it prevented secondary shortening of the twitch. Continuous stimulation reduced tension loss but was, perhaps, less effective than intermittent stimulation. 7. Twitch-tetanus ratio increased with denervation with little spontaneous reversal later. Stimulation at all frequencies reduced the ratio, but it did not reach normal values. 8. Isotonic shortening velocity was measured in many of the muscles. Maximum velocity was estimated and normalized by muscle length.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Human respiratory muscle actions and control during exercise.

We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (Wmax) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of Wmax as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. DeltaVrc,a/DeltaVab was constant and independent of Wmax. Thus we used DeltaVab/time as an index of diaphragm velocity of shortening. From QB to 70% Wmax, diaphragmatic pressure (Pdi) increased approximately 2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was approximately 0 during QB but was equal to and 180 degrees out of phase with rib cage muscle pressure at all percent Wmax. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% Wmax there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180 degrees out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion.

Abdominal Muscles↗

Monkey cerebral arterial relaxation caused by hypercapnic acidosis and hypertonic bicarbonate.

In helical strips of Japanese monkey cerebral arteries contracted with vasoconstrictors, applications of high CO2 (15% compared with 5% CO2 in control media) and hypertonic NaHCO3 (50 mM) produced relaxations. Similar relaxations were also obtained in human cerebral arterial strips. Hypercapnia increased PCO2 and resulted in acidosis in the bathing media, and the addition of NaHCO3 restored the pH to normal with high PCO2 and increased the osmotic pressure. The relaxant responses were not influenced by endothelium denudation and treatment with indomethacin. The hypercapnia-induced relaxation was suppressed by ouabain but was unaffected by amiloride. On the other hand, hypertonic bicarbonate-induced relaxations were inhibited by ouabain as well as by amiloride. Removal of Na+ from the bathing media abolished the hypercapnia-induced relaxation but did not alter the hyperosmolar relaxation. In contrast to hypertonic NaHCO3, isotonic bicarbonate solutions contracted the arterial strips by neutralizing the pH under hypercapnia. It may be concluded that relaxations elicited by hypercapnic acidosis are associated with a fall of extracellular pH and an activation of the electrogenic Na+ pump, and those caused by hyperosmolarity are due to stimulation of the Na(+)-H+ exchange and the Na+ pump. Endothelium-derived vasoactive substances and cyclooxygenase products do not appear to be involved in these relaxations of monkey cerebral arteries under the experimental conditions used.

Acidosis↗

Accounting for the Gregg effect in tetanised coronary arterial pressure-flow relationships.

OBJECTIVE: Myocardial contraction shifts the diastolic coronary pressure-flow relationship to lower flows at any given pressure, the amount of shift being determined primarily by the contractile level. A portion of this shift may be attributable to the Gregg effect. The purpose of this study was to quantify the influence of the Gregg effect and thereby demonstrate the pure effect of activation at a constant contractile level on the pressure-flow relationships. METHODS: It was first shown in beating canine interventricular septa that transverse stiffness induced by small high frequency indentations transverse to the plane of the tissue was an index of contractility. At constant perfusion pressure and preload, there was an inverse relationship between peak transverse stiffness and contractile level (induced by graded doses of 2,3-butanedione monoxime) for both isotonic and auxotonic contractions. A Gregg effect was next verified by showing a linear dependence between transverse stiffness and perfusion pressure during ryanodine induced tetanizations. Finally, the relationship between changes in flow and transverse stiffness was determined from diastole to tetany at two contractile levels. These relationships suffice to quantify the Gregg effect. RESULTS: Correcting for the Gregg effect from the transverse stiffness measurements obtained concomitantly with previously reported pressure-flow data in six specimens showed the following: using a linear fit to the pressure-flow data, the mean slope of the diastolic pressure-flow relationships decreased from 0.88 to 0.81 and 0.74 ml.min-1 x mmHg-1 during tetanisation at normal and reduced contractile levels, respectively. Correcting for the Gregg effect decreased the tetanised slopes to intermediate values of 0.85 and 0.79 ml.min-1 x mmHg-1, respectively. CONCLUSIONS: A small but clearly discernible portion of the shift in tetanised pressure-flow relationships is attributable to the Gregg effect. Similar conclusions pertained when quadratic regressions were fitted to the pressure-flow data.

Animals↗