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The potentiation of cardiodepressant and hypotensive effects of bradykinin by enalapril and captopril both in vitro and in vivo.

1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.

Anesthesia↗

Oxidation of acetate and octanoate and its relation to glucose metabolism in contracting porcine carotid artery.

The oxidation of octanoate and acetate was measured in segments of porcine carotid arteries to ascertain whether the oxidation of exogenous fatty acid substrates (acetate and octanoate) is augmented during contraction induced by K(+)-depolarization. The oxidation of acetate increased from 7 +/- 1 to 14 +/- 2 nmol/min/g (P < 0.01) during sustained isometric contraction. Octanoate oxidation increased from 11 +/- 1 to 14 +/- 1 nmol/min/g (P < 0.05). The rate of oxidation of neither acetate nor octanoate was affected by the presence or absence of glucose either in resting or contracting arteries Acetate or octanoate oxidation could account for the majority of O2 consumption during contraction. Octanoate but not acetate inhibited glucose uptake and glycolysis in resting muscles. In contrast to augmented acetate and octanoate metabolism during contraction, there was a "down-regulation" of glucose metabolism in contracting muscles as evidenced by a decrease in the rate of glucose uptake, glycolysis and lactic acid production during sustained isometric contraction. Thus, contractile activation of vascular smooth muscle is associated with a shifting pattern of substrate utilization. Exogenous acetate or octanoate can serve as the primary oxidative substrate during sustained isometric contraction.

Acetates↗

Recruitment stability in masseter motor units during isometric voluntary contractions.

Recruitment of single motor units (SMUs) of the masseter muscle was studied using macro representation (MacroRep) as the indicator of motor unit size. When subjects followed a slow isometric force ramp, units were usually recruited in order of MacroRep size. However, pooling the data from repeated ramps in the same subject resulted in a weak relationship between MacroRep size and force recruitment threshold, probably due to marked variations in the relative contributions of the jaw muscles, and varying levels of cocontraction, in the development of total bite force in each ramp. The force recruitment thresholds of individual SMUs showed marked variability, but recruitment threshold stability was improved when expressed as a percentage of maximum surface electromyographic (SEMG) activity in the ipsilateral masseter. Therefore the SEMG recruitment threshold was concluded to be a more stable and accurate indicator of the SMU's position in the recruitment hierarchy in a given muscle. It was concluded that SMUs in masseter are recruited according to the size principle, and that when investigating recruitment in jaw muscles, SEMG recruitment threshold should be used in preference to force recruitment threshold.

Differential Threshold↗

Muscle fibre conduction velocity during fatiguing and nonfatiguing isometric arm contractions.

In the present study the behaviour of muscle fibre conduction velocity was investigated by means of a new method for the continuous registration from surface EMGs. During fatiguing isometric arm contractions at 40% of maximum voluntary contraction close relations between conduction velocity and spectral parameters of surface EMG were found. In short nonfatiguing contractions at 15%, 30%, 45%, 60%, and 75% of maximum force no significant differences of conduction velocity could be observed. An example of continuous registration of the parameters is given.

Action Potentials↗

Effects of captopril on cold pressor test responses in normotensive and hypertensive subjects.

The aim of this study was to evaluate the effects of short-term captopril administration on the response to cold pressor testing in normotensive and hypertensive subjects. Cold pressor testing was performed in 15 normotensive subjects and 15 hypertensive patients before and 90 minutes after captopril administration. Blood pressure and heart rate were measured before testing and at one-minute intervals from the beginning of cold pressor testing. Systolic time intervals were also assessed before and after testing. Captopril did not affect pressor responses to cold pressor testing in normotensive subjects or hypertensive patients. Basal heart rate (before testing) did not change, despite the decrease in blood pressure and showed a smaller increase in response to cold pressor testing in normotensive subjects, suggesting that captopril might interfere with arterial baroreflexes. The systolic time intervals were not modified by captopril except isometric contraction time; its basal value was reduced by captopril in both normotensive subjects and hypertensive patients. Cold exposure caused a similar increase in isometric contraction time before and after captopril in normotensive subjects, and the increase in isometric contraction time in hypertensive patients was greater. These findings suggest that captopril did not affect cardiac performance, indeed improving it, at least in basal conditions.

Adult↗

Effects of neck extensor muscles fatigue on balance.

OBJECTIVE: Measure the effects of cervical extensor muscle isometric contraction on cervical surface electromyographic spectral shift and balance in healthy subjects. DESIGN: Experimental within-subject design. BACKGROUND: Postural instability can be induced by mechanically stimulating cervical muscle spindles. Postural changes are also observed in individuals who suffer from chronic neck pain or whiplash injury. Furthermore these subjects appear to experience neck musculature fatigue more quickly, which in turn not only affects the neck function but also seems to affect the balance in a standing posture. METHODS: Using a force platform, balance was measured, in 10 blindfolded college students before and after isometric voluntary contraction in neck extension at 5% and 25% maximum voluntary isometric contraction for a period of 5, 10 and 15 min. Paired posturographic data were analysed for differences. Control measurements were performed on the same subjects by measuring balance before and after subjects sitting quietly for 5, 10 and 15 min without performing isometric contraction. RESULTS: The results indicate that a 25% maximal isometric contraction of the neck extensors for 10 and 15 min duration produced significant changes in some posturographic parameters in young healthy males. Furthermore, this contraction also produced a significant cervical muscle electromyography median frequency spectrum shift of the lower frequencies. CONCLUSIONS: Balance was affected by 15 min of 25% maximal isometric contraction of the extensor cervical muscles. Posturographic parameters affected are similar to parameters observed in subjects that have suffered a whiplash injury. RELEVANCE: This study contributes to our understanding of functional aspects of cervical muscle fatigue. The similarity of results with other studies performed on subjects suffering from chronic neck pain and from whiplash injuries may suggest a similar cause for loss of postural control. Ultimately, this may help us in developing objective evaluation procedures for subjects suffering from neck complaints.

Adult↗

Spatial distribution of vastus lateralis blood flow and oxyhemoglobin saturation measured at the end of isometric quadriceps contraction by multichannel near-infrared spectroscopy.

Muscle blood flow (MBF) and muscle oxygen saturation (SmO(2)) were measured at eight locations (four proximal, four distal) over a 4 x 8 cm(2) area of the vastus lateralis at rest and immediately after isometric, maximal quadriceps contraction using multichannel, frequency-domain, near-infrared spectroscopy. A venous occlusion was applied 20 s before the end of the exercise, so that the venous-occlusion-induced increase in total hemoglobin was recorded without any delay after the end of the exercise. Therefore, we were able to investigate the relationship between the exercise-induced changes in vastus lateralis MBF and SmO(2). After exercise, MBF increased significantly at each measured location. Comparing the MBF values measured at the end of exercise in the proximal and distal regions, we observed that only one proximal region had a significantly higher MBF than the corresponding distal one. The maximum desaturation measured during exercise was positively correlated with the postexercise to pre-exercise MBF ratio in both the proximal (P=0.016) and distal (P=0.0065) regions. These data confirm that frequency-domain tissue oximeters are noninvasive, powerful tools to investigate the spatial and temporal features of muscle blood flow and oxygenation, with potential applications in areas of pathophysiology.

Adult↗

31P NMR magnetization-transfer measurements of ATP turnover during steady-state isometric muscle contraction in the rat hind limb in vivo.

31P NMR magnetization-transfer measurements have been used to measure the flux between ATP and inorganic phosphate during steady-state isometric muscle contraction in the rat hind limb in vivo. Steady-state contraction was obtained by supramaximal sciatic nerve stimulation. Increasing the stimulation pulse width from 10 to 90 ms, at a pulse frequency of 1 Hz, or increasing the frequency of a 10-ms pulse from 0.5 to 2 Hz resulted in an increase in the flux which was an approximately linear function of the increase in the tension-time integral. The flux showed an approximately linear dependence on the calculated free cytosolic ADP concentration up to an ADP concentration of about 90 microM. The data are consistent with control of mitochondrial ATP synthesis by the cytosolic ADP concentration and indicate that the apparent Km of the mitochondria for ADP is at least 30 microM.

Adenosine Triphosphate↗

Neuropeptide Y-like substances are released from the rostral brainstem of cats during the muscle pressor response.

1. In this study, the release of immunoreactive neuropeptide Y (NPY)-like substances (irNPYs) was measured from the rostral brainstem in response to fatiguing isometric contractions of the hindlimb muscle of cats anaesthetized with alpha-chloralose. 2. The irNPYs were measured using a solid phase autoradiographic immunoassay. NPY antibody-coated glass microelectrodes were inserted stereotaxically into the rostral brainstem during rest and contractions. Control procedures such as passive leg flexing, stimulation of the central end of the cut tibial nerve, brief repeated carotid occlusions and carotid sinus nerve stimulations were performed to determine whether patterns of release of irNPYs were specific to the pathways activated during the muscle pressor response. 3. During isometric contractions, the mean arterial blood pressure (MABP) and heart rate (HR) increased by 60-70 mmHg and 15-20 beats min-1, respectively. Only the brief carotid occlusions caused a similar increase in MABP and HR. 4. During isometric contractions, less irNPYs were released from sites in the lateral reticular nucleus, lateral tegmental field and vestibular nuclei at a level in the brainstem 4.0-4.4 mm rostral to the obex. In contrast, irNPYs were released from sites near the lateral tegmental field and nucleus ambiguus at a more caudal level tested (1.3 mm anterior to the obex) in response to contractions. Brief carotid occlusions caused a release of irNPYs from the lateral reticular nucleus on the contralateral side of the brainstem (at 3.5 mm anterior to the obex). None of the other procedures resulted in a release of irNPYs from these sites in the brainstem. 5. These data indicate there are differences in the patterns of release of irNPYs in response to activation of reflex pathways which increase arterial pressure. Given the sites in the rostral brainstem where irNPYs were released, irNPYs may be involved with the central regulation of arterial pressure during the muscle pressor response.

Animals↗

Instantaneous view of actomyosin structure in shortening muscle.

In the previous study), utilizing the rapid-freeze technique for electron microscopy, a new type of actomyosin assembly was reported to occur during isometric contraction. In this study, we have developed a new freezing apparatus which permits rapid freezing of the "isotonically-shortening" muscle at high shortening velocity, allowing simultaneous measurement of its tension and length. Using glycerinated rabbit skeletal muscle rapidly frozen with this system, we have compared the freeze-substituted images of the actomyosin assembly in the shortening muscle at various tension levels with those in isometrically-contracting muscle. The optical diffraction patterns obtained from whole A bands and from single actin filaments decorated with crossbridges have revealed that the unique actomyosin assembly formed in isometrically-contracting muscle is maintained even during high-velocity shortening under near-zero load.

Actomyosin↗

Muscle spindle response at the onset of isometric voluntary contractions in man. Time difference between fusimotor and skeletomotor effects.

1. Impulses in single muscle afferents were recorded from the median nerves of waking human subjects with percutaneously inserted tungsten needle electrodes. During isometric voluntary contractions, unitary discharges were analysed from muscle spindle endings in the wrist and finger flexor muscles and the electromyographic activity from these muscles was recorded simultaneously.2. When the subject activated the muscle portion in which a spindle was located, the afferent discharge increased in spite of the mechanical unloading effects of the skeletomotor contraction indicating a concomitant fusimotor activation. This was valid for slowly rising contractions as well as small fast rising twitches.3. The time of onset of spindle acceleration was determined in relation to the time of onset of the electromyographic activity for thirty-one units studied altogether in more than seven hundred contractions. It was found that spindle acceleration regularly occurred after the onset of the electromyographic activity.4. There was a considerable variation from one test to the other, for the individual units, with regard to the exact time of onset of spindle acceleration, although spindle acceleration occurred mostly within 0.5 sec after the onset of the electromyographic activity in sustained contractions and within 0.1 sec in small fast rising twitches. It was not possible to assess to what extent this variation was accounted for by variations in the mechanical unloading effects of the skeletomotor contraction or variations in the timing of the fusimotor outflow.5. For many units, spindle acceleration did not occur until 10-50 msec after the onset of the skeletomotor contraction. This time is of the same order of magnitude as the time difference in latency from the spinal cord to the recording points in the two systems, as estimated from reasonable assumptions.6. It was concluded that the fusimotor system does not participate in the initiation of voluntary contractions in man, but that the skeletomotor activity is initiated by descending impulses from supraspinal structures and their effects on the neuronal organization within the spinal cord.7. The fact that fusimotor activation occurs also in very small and short lasting twitches, when spindle acceleration must have a negligible influence on the skeletomotor outflow, suggests that the fusimotor and the skeletomotor systems are rigidly co-activated in voluntary contractions.8. The finding that spindle acceleration does not occur until 10-50 msec after the onset of the electromyographic activity suggests that there is an approximately simultaneous onset of the fusimotor and the skeletomotor outflows from the spinal cord.

Adult↗

Further examination of the effects of ageing on the adrenoceptor responsiveness of the rat vas deferens.

Age-related changes in presynaptic alpha 2-adrenoceptors were investigated in prostatic and epididymal portions of vasa deferentia from young adult (2-3 months) and old (24-29 months) Sprague-Dawley rats, using the alpha 2-selective agonists xylazine and clonidine. In prostatic portions the inhibitory effects of clonidine against the isometric contractions to single pulse field stimulation were complicated by a postsynaptic action in old animals, but in epididymal portions in the presence of nifedipine both xylazine and clonidine were 3 times less potent in old rats. However, there were no significant differences between young and old in the potency of xylazine at inhibiting the overflow of tritium or the isometric contraction evoked by 5 Hz stimulation for 3 min in tissues pre-incubated with [3H]noradrenaline. It is suggested that there is reduced responsiveness of presynaptic alpha 2-adrenoceptors in the vas deferens of old rats, but that this can only be demonstrated using a sensitive measure of the presynaptic potency of agonists: the isometric contraction to a single stimulus.

Aging↗

Intermuscle differences in activation.

The objective of this study was to investigate differences within individual subjects in the ability to activate the quadriceps, plantar flexors (PF), dorsiflexors (DF), and elbow flexors (EF) during isometric contractions. Twelve male subjects performed submaximal and maximal voluntary isometric contractions, and maximal tetanic contractions were also induced by electrical stimulation. The interpolated twitch technique was used to gauge the extent of muscle inactivation or inability to produce maximum force. Measurements included torque output, absolute and relative rate of force development (RFD), and percentage of muscle inactivation. The quadriceps exceeded all other muscle groups in voluntary and tetanic torque output, voluntary absolute RFD, and absolute and relative tetanic RFD. The quadriceps also exceeded the PF and DF in voluntary relative RFD and had greater muscle inactivation (15.5%) than the EF (5.0%), PF (5.0%), and DF (1.3%). Although the higher RFD may suggest a higher percentage of type II fibers in the quadriceps, their higher threshold of recruitment leads to greater difficulty in fully activating the quadriceps.

Adult↗

The effect of nickel chloride on the isolated hemidiaphragm of the rat.

1. NiCl2 (cumulative concentrations of 0.56-1.91 mmol 1(-1)) produced concentration-dependent depression of tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of isometric contraction of the isolated rat hemidiaphragm, during direct subtetanic (DST) electrical stimulation, only. EC50 values for NiCl2-induced depression of Td and Dt/dt max were 0.88 +/- 0.06 and 0.83 +/- 0.13 mmol 1(-1), respectively. NiCl2 did not significantly change either parameter of the isometric contraction during direct single-pulse (DSP) electrical stimulation. 2. Maximal depression of Td and dT/dt max, produced by a single concentration of NiCl2 (1 mmol 1(-1)) during DST electrical stimulation was obtained 20 min after addition of the drug in the bathing medium. 3. In the normal Tyrode solution, addition of CaCl2 (final concentration of 5.86 mmol 1(-1)) almost completely antagonized the depressant effect of NiCl2 (1 mmol 1(-1)) on Td and dT/dt max during DST electrical stimulation. In the calcium-free solution, the depression both of Td and dT/dt max produced by NiCl2 (1 mmol 1(-1)) was significantly more pronounced in comparison with the effect of NiCl2 in the normal Tyrode solution. 4. L-calcium channel activator, Bay K 8644 (25 mumol 1(-1)), significantly potentiated both Td and dT/dt max during DST electrical stimulation, but NiCl2 (1 mmol 1(-1)) decreased both parameters of the isometric contraction even in the presence of this concentration of Bay K 8644. On the other hand Bay K 8644 (25 mumol 1(-1)) did not antagonize NiCl2-induced depression of Td and dT/dt max. 5. Verapamil (2.5 mumol 1(-1); 45 min of incubation) and lidocaine (0.10 mmol 1(-1); 30 min of incubation) significantly potentiated the depression of Td and dT/dt max, produced by NiCl2 (1 mmol 1(-1), during DST electrical stimulation. The addition of CaCl2 (final concentration of 7.20 mmol 1(-1)) in the bathing medium only partially antagonized the depressant synergistic action of both verapamil or lidocaine and NiCl2 on Td and dT/dt max. 6. Forskolin (cumulative concentrations of 2.60-44.20 mumol 1(-1)) fully antagonized NiCl2-induced depression of both Td and dT/dt max; propranolol (1 mumol 1(-1)) did not abolish this antagonizing action of forskolin. Also, NiCl2 (cumulative concentrations of 0.56 -1.54 mmol 1(-1)) did not change potentiating effect of forskolin (23.4 mumol 1(-1)).(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Eccentric exercise augments the cardiovascular response to static exercise.

High-force eccentric exercise induces neuromuscular dysfunction and may augment the cardiovascular response to exercise. This investigation sought to determine whether changes in strength and sense of force following high-force eccentric exercise alter heart rate and blood pressure responses during isometric contractions. Subjects (4F,6M) performed 50 maximum resistance eccentric actions with one arm (ECC arm). Contractions at 10% of the ECC arm maximum were held for 7 min on two pre-exercise days. The force output perceived to be the same as 10% of the pre-exercise maximum was determined using a force matching task. This force, 35.6, 27.2, and 21.1% lower on days 1, 3, and 5 post-exercise, was held during isometric contractions on these days, respectively. Despite a lowering of absolute contraction force, heart rate (P < 0.05) and blood pressure (P < 0.001) responses during contractions using the ECC arm were consistently elevated relative to the control arm. However, subjects perceived that they were exerting forces similar to those achieved before eccentric exercise-induced neuromuscular dysfunction. These findings suggest that perceived effort following strength loss induced by mechanically stressful exercise dictates the cardiovascular responses during isometric contractions.

Adolescent↗

[Effects of nicardipine on the spontaneous beat of isolated atria of guinea pigs].

Nicardipine was found to produce a concentration-dependent depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. It also depressed the atrial rate of the isolated, spontaneously beating atria of the guinea-pig. The effect of the increasing concentrations of nicardipine on the heart rate was negligibly weaker than its effect on the isometric contraction. A time-dependent depression of the isometric contraction and the atrial rate after the addition of a single dose of nicardipine was also found up to the 10th min. Calcium almost completely, isoprenaline completely and aminophylline partially antagonized the depressive action of nicardipine on the isometric contractility of the atria. Only isoprenaline antagonized the negative chronotropic action of higher doses of nicardipine. It is possible that these substances restore the contractility by compensating the calcium balance, previously changed by nicardipine, or by producing an increase in the intracellular cAMP content (isoprenaline and aminophylline).

Aminophylline↗