Changes in maximal exercise ventilation and breathing pattern in boys during growth: a mixed cross-sectional longitudinal study

The aim of this mixed cross-sectional longitudinal study covering a total age range of 11-17 years, i.e. the entire pubertal growth period, was (1) to specify the changes in maximal breathing pattern during incremental exercise; (2) to determine what parts of the changes are due to anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength; and (3) to determine if the role of these variables is identical before, during and after pubertal growth spurt. This study was conducted in 44 untrained schoolboys separated into three groups, with an initial age of 11.2 +/- 0.2 years for group A, 12.9 +/- 0.25 years for group B, and 14.9 +/- 0.26 years for group C. These children were subsequently followed for 3 years, during the same time period each year. The maximal inspiratory and expiratory pressures (PI max and PE max) were used as an index of the respiratory muscle strength. During an incremental exercise test, maximal ventilation (VE max), tidal volume (VT max), breathing frequency (fmax), inspiratory and expiratory times (tI max and tE max) and mean inspiratory flow (VT/tI max) were measured at maximal oxygen uptake (VO2max). Our study showed that there was a marked increase with age in VE max, VT max, and VT/tI max, and no significant changes in fmax, tI max and tE max. PI max and PE max showed a general trend towards an increase between 11 and 17 years. The study of the linear correlations between maximal breathing pattern and the anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength showed that, in the three groups of children, (1) lean body mass was the major determinant of VE max, VT max and VT/tI max and the relationships were significantly different before, during and after the pubertal growth spurt; (2) physical fitness was the main determinant of tI max, tE max and fmax before and after the pubertal growth spurt; and (3) maximal respiratory strength did not play a significant role. In conclusion, this mixed cross-sectional longitudinal study showed, at maximal exercise, a significant increase in VE max during growth due only to a significant increase in VT max and VT/tI max, and that the relationships of anthropometric characteristics and physical fitness with maximal breathing pattern change during growth.     

Studies on right ventriculal function of clinical cases (author''s transl)

Total lactate dehydrogenase (LDH) activity and LDH isozyme pattern were studied in muscle biopsies obtained from m. vastus lateralis after 1) "aerobic" training performed as interval and extreme distance running, respectively (3 subjects); and 2) "anaerobic" training for two months, carried out as repeated maximal bursts of approximately 1 min running (6 subjects). After the "anaerobic training" no changes in LDH properties could be detected, although running performance improved. The extreme distance running resulted in a decrease in total LDH activity and an increase in relative activity of the heart specific isozymes. A relationship was also shown between the relative activity of these isozymes and the training distance covered. The relatively more aerobic prevailing during distance running as compared to "anaerobic training" were proposed to decrease muscle specific subunits and/or increase synthesis of heart specific subunits in both muscle fiber types. This suggestion was supported by isozyme analysis of lyophilized and dissected single muscle fibres.     

Kinetic parameters of lactate dehydrogenase in liver and gastrocnemius determined by three quantitative histochemical methods

We determined the Michaelis constant (K(m)) and maximal velocity (Vmax) of lactate dehydrogenase (LDH) in periportal hepatocytes and skeletal muscle fibers by three different histochemical assay methods. Unfixed sections of mouse liver and gastrocnemius were incubated at 37C either on substrate (L-lactate)-containing agarose gel films or in aqueous assay media with and without 18% polyvinyl alcohol (PVA) as a tissue protectant. The absorbances of the formazan final reaction products were continuously measured at 584 nm in the cytoplasm of individual cells as a function of incubation time, using an image analysis system. The kinetic parameters of purified rabbit skeletal muscle LDH incorporated into polyacrylamide gel sections were similarly determined. The intrinsic initial velocities (vi) of LDH, corrected for "nothing dehydrogenase," were determined as described in the previous article. The Km and Vmax were calculated from Hanes plots of s/vi on L-lactate concentration (s). The Km values obtained with three assay methods were similar and in the range of 21.1-21.9 mM for pure LDH, 8.62-13.5 mM for LDH in mouse periportal hepatocytes, and 13.3-17.9 mM for LDH in mouse skeletal muscle fibers. The Vmax values determined on agarose gel substrate films and in aqueous assay media without PVA were in good agreement but were 53-65% lower when 18% PVA was included in the medium. These results indicate that catalytic center activity kcat of LDH is retarded by the high viscosity of PVA media because PVA hardly inhibited the enzyme. The K(m) values of LDH determined histochemically in skeletal muscle fibers and periportal hepatocytes were respectively three to five times and two to three times higher than those determined biochemically. These differences may be due to interactions of LDH with intracellular components.     

Force-velocity properties and myosin light chain isoform composition of an identified type of skinned fibres from rat skeletal muscle

Force-velocity relations, myosin heavy chain (MHC) and myosin light chain (MLC) isoform composition of single skinned fibres from rat plantaris muscle were determined. In fibres containing the same (2X) isoform of myosin heavy chain, several parameters derived from the force-velocity relation and isometric force (Po) were tested for relation with the fibre content in alkali myosin light chain (MLC) isoforms. Whereas maximum shortening velocity was found to be proportional to the relative content in the 3f isoform of alkali MLC, velocity of shortening at 5% relative load, maximum power output, and Po were not. These results strengthen the idea that, in mammalian skeletal fibres, alkali MLC isoforms modulate shortening velocity at zero load, but suggest that they do not control the contractile behaviour at loads higher than zero.     

Gender comparisons of the mechanomyographic responses to maximal concentric and eccentric isokinetic muscle actions

PURPOSE: The purpose of this study was to determine whether there is a gender difference in the velocity-related patterns of mechanomyographic (MMG) responses to maximal isokinetic concentric (CON) and eccentric (ECC) muscle actions. METHODS: Adult males (N = 15) and females (N = 16) performed maximal CON and ECC muscle actions of the leg extensors on a calibrated Cybex 6000 dynamometer at velocities of 30, 90, and 150 degrees.s-1. MMG was detected by a piezoelectric crystal contact sensor placed over the vastus lateralis muscle. RESULTS: The results indicated that there were decreases in CON peak torque (PT) across velocities, while ECC PT remained constant with increasing velocity for both genders. MMG amplitude increased significantly (P < 0.05) with velocity in both the males and females for CON and ECC muscle actions. There was a gender difference in the velocity-related patterns of MMG responses to maximal isokinetic CON muscle actions; however, there was no gender difference in the pattern of ECC MMG responses. CONCLUSIONS: The gender difference in CON MMG responses may be attributed to the greater percent decline in CON PT across velocity for the females than the males. In addition, the males displayed greater CON and ECC MMG amplitudes at all muscle action velocities than the females, possibly because of gender differences in muscle mass and/or thickness of the adipose tissue layer.     

Molecular weight of cytoplasmic malate dehydrogenase, mitochondrial malate dehydrogenase and lactate dehydrogenase of a freshwater catfish

The multiple molecular forms of cytoplasmic malate dehydrogenase (cMDH), mitochondrial malate dehydrogenase (mMDH) and lactate dehydrogenase (LDH) were studied in the liver and skeletal muscle of the freshwater catfish, Clarias batrachus. There were two electrophoretically distinguishable bands (AA and BB) of cMDH and mMDH which suggests that they are apparently encoded at two gene loci (A and B) in both the tissues. However, the presence of a single band (LDH-1) of LDH in liver and double bands (LDH-1 and LDH-2) in skeletal muscle in which LDH-2 was predominant reflects the differential expression of LDH genes in different metabolic tissues to meet the requirement of energy production. The AA isoform (74 kd) of liver cMDH was smaller than those of the AA form (110 kd) of skeletal muscle. In contrast, the BB isoform of liver (42 kd) and skeletal muscle (54 kd) were more or less similar in size. Unlike the case of cMDH, the molecular weight of AA isoform (115 kd) of liver mMDH was higher than those of the AA form (87 kd) of skeletal muscle. Whereas the molecular weight of BB isoform (58 kd) of liver was in proximity to the weight of BB form (44 kd) of skeletal muscle mMDH. The size of AA isoform (74 kd) of liver cMDH was smaller, while the AA isoform (110 kd) of skeletal muscle was larger as compared to AA form of mMDH in the liver (115 kd) and skeletal muscle (87 kd). But the size of BB isoform of both the isozymes was almost equal in these metabolic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin 1alpha stimulates lactate dehydrogenase A expression and lactate production in cultured porcine sertoli cells

By using cultured porcine Sertoli cells as a model, the action of interleukin 1alpha (IL-1alpha) on lactate production and the site of this action were studied. IL-1alpha stimulated Sertoli cell lactate production in a time- and dose-dependent manner (with a half-maximal effect [ED50] of 6 pM). Two major sites involved in IL-1alpha action were identified. First, IL-1alpha was shown to increase the uptake of glucose substrate in a time- and dose-dependent manner. The maximal effect, with an ED50 of 10 pM, was observed after 24 h of treatment. Second, IL-1alpha increased the activity of the lactate dehydrogenase (LDH) A4 isoform, which is involved in the conversion of pyruvate into lactate. This increase in LDH A4 activity was detected at 12 h and was maximal, with an ED50 of 9 pM, after 24-h treatment with IL-1alpha. The increase was related to an increase in LDH A4 expression, since IL-1alpha stimulated LDH A mRNA (size: 1.5 kilobases, evidenced through Northern blotting analysis) in a dose- and time-dependent manner. Assuming that IL-1alpha might be produced in the seminiferous tubules by both Sertoli and germ cells, which utilize lactate for their energy metabolism, we suggest that these results together show 1) that the cytokine may represent a signal in the metabolic cooperation existing between Sertoli cells and germ cells, and 2) that a redistribution of LDH isoforms in favor of LDH A4 under IL-1alpha control is a key mechanism(s) in such cooperation used by germ cells to enhance lactate production in Sertoli cells.     

Myosin and troponin changes in rat soleus muscle after hindlimb suspension

We examined the myosin heavy-chain (MHC), troponin T (TnT), and troponin I (TnI) isoform composition in the rat soleus muscle after 21 days of hindlimb suspension using electrophoretic and immunoblotting analysis with specific monoclonal antibodies. The suspended soleus showed a shift in the MHC isoform distribution with a marked increase (from 1.0 to 33%) in the relative amount of type IIa and IIx MHC and a corresponding decrease in type I MHC. However, type IIb MHC, which represents a major component in fast-twitch muscles, was not detected in suspended soleus muscles. TnT and TnI isoform composition was also changed with the appearance of fast-type TnI and TnT bands. However, a high-mobility TnT band, which represents a major component in fast-twitch muscles, was not expressed in suspended soleus. These isoform transitions may be related to the increased maximal velocity of shortening and higher calcium sensitivity previously reported in the rat soleus after hindlimb suspension.     

Biomechanical characteristics of unconditioned and conditioned latissimus dorsi muscles used for cardiocirculatory assistance

An understanding of the biomechanical characteristics of striated skeletal muscles involved in cardiocirculatory assistance is a prerequisite to assess their efficacy and to evaluate their haemodynamic benefits. Six goats had their latissimus dorsi muscles evaluated by isometric strain gauge testing. Total tension, and both active and passive force development at different preloads were measured. The relationship between muscle impedance and starting length was also studied. Four additional muscles were submitted to isometric and isotonic strain gauge testing after 3 months of chronic electrical stimulation (Broussais Hospital protocol) with the contralateral muscle serving as a control. In isometric testing, both conditioned and unconditioned goat latissimus dorsi displayed a Frank-Starling length-tension curve, and a linear relationship between muscle impedance and starting length was found. Chronic stimulation preserved muscle mass and isometric force. Transformed muscles showed a mean 59% reduction of maximal shortening velocity; means (s.d.) residual shortening velocity at maximal work and power output was 0.17(0.07) m/s. The work and power output were both reduced 65% after stimulation, and the residual maximal power at optimal preload varied from approximately 7.7 and 9.6 W/kg. It is concluded that, following the Broussais protocol, the goat latissimus dorsi muscle retained mass and most of its isometric force-generating capacity, but lost significant work and power potential. The residual power output did not, however, preclude the possibility of a significant cardiocirculatory contribution, providing that the conditions for optimal energy transduction are adequately delineated.     

Reduced mechanical efficiency in chronic obstructive pulmonary disease but normal peak VO2 with small muscle mass exercise

We studied six patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 1.1 +/- 0.2 L, 32% of predicted) and six age- and activity level-matched control subjects while performing both maximal bicycle exercise and single leg knee-extensor exercise. Arterial and femoral venous blood sampling, thermodilution blood flow measurements, and needle biopsies allowed the assessment of muscle oxygen supply, utilization, and structure. Maximal work rates and single leg VO2max (control subjects = 0.63 +/- 0.1; patients with COPD = 0.37 +/- 0.1 L/minute) were significantly greater in the control group during bicycle exercise. During knee-extensor exercise this difference in VO2max disappeared, whereas maximal work capacity was reduced (flywheel resistance: control subjects = 923 +/- 198; patients with COPD = 612 +/- 81 g) revealing a significantly reduced mechanical efficiency (work per unit oxygen consumed) with COPD. The patients had an elevated number of less efficient type II muscle fibers, whereas muscle fiber cross-sectional areas, capillarity, and mitochondrial volume density were not different between the groups. Therefore, although metabolic capacity per se is unchanged, fiber type differences associated with COPD may account for the reduced muscular mechanical efficiency that becomes clearly apparent during knee-extensor exercise, when muscle function is no longer overshadowed by the decrement in lung function.     

Lactate dehydrogenase activity and isoform distribution in the rat pelvic ganglion: effects of diabetes and bladder outlet obstruction

We have previously shown that the intramural motor nerves in the rat bladder can function in anoxic conditions. The present study aims to explore the distribution and activity of lactate dehydrogenase (LDH), the key enzyme for ATP generation in anoxia. The activity and isoform distribution pattern of LDH was studied in pelvic ganglia from male and female rats. A histochemical investigation showed that the LDH activity was intense in the ganglion cells, and weak in the other tissue components (nerve bundles, connective tissue). The male pelvic ganglion weighted 55% more than the female pelvic ganglion, the enzyme activity per unit ganglion weight was 60% higher and the total LDH activity was 155% higher. The isoform distribution was similar, with M4 being dominant isoform, followed by M3H. Infravesical outlet obstruction in the female rat induced a threefold increase in ganglion weight, and the total LDH activity increased twofold. In this hypertrophic female ganglion a decreased relative amount of M4, and an increased amount of MH3, was found. Diabetes in the male rat had no effect on ganglion weight or its contents and isoform distribution of LDH.     

Myosin essential light chain isoforms modulate the velocity of shortening propelled by nonphosphorylated cross-bridges

The differential effects of essential light chain isoforms (LC17a and LC17b) on the mechanical properties of smooth muscle were determined by exchanging recombinant for endogenous LC17 in permeabilized smooth muscle treated with trifluoperazine (TFP). Co-precipitation with endogenous myosin heavy chain verified that 40-60% of endogenous LC17a could be exchanged for recombinant LC17a or LC17b. Upon addition of MgATP in Ca2+-free solution, recombinant LC17 exchange induced slow contractions unaccompanied by regulatory light chain (RLC) phosphorylation only in TFP-treated, but not in untreated, permeabilized smooth muscle; the shortening velocity and rate of force development were approximately 1.5 and 2 times faster, respectively, in response to LC17a than LC17b. Additional incubation with recombinant, thiophosphorylated RLC increased the shortening velocity, independent of the LC17 isoform exchanged. The LC17-induced contractions of TFP-treated muscles were abolished by prior addition of nonphosphorylated RLC. We suggest that LC17 stiffens the lever arm of myosin and, in the absence of regulation by RLC, permits cross-bridge cycling without requiring RLC phosphorylation. Our results are compatible with nonphosphorylated RLC acting as a repressor and with LC17 isoforms modulating the MgADP affinity and, consequently, rate of cooperative cycling of nonphosphorylated cross-bridges.     

The rat suspension model is also a good tool for inducing muscle hyperactivity

The aim of the present study was to investigate changes in the mechanical characteristics of the rat epitrochlearis muscle as a result of a period of hyperactivity. A tail suspension model was used to impose postural activity in the forelimb musculature with the intention of inducing a relative slowness in the fast epitrochlearis muscle. A method of dual-controlled releases was used to obtain force-velocity and tension-extension relationships characterizing muscle mechanics. Results showed that: (1) mechanical characteristics are that of a fast-twitch muscle and (2) suspension induces a decrease in the maximal shortening velocity and a decrease in the compliance of series elastic elements. Changes in fibre type proportions are consistent with these mechanical adaptations. This demonstrates that an usual model of muscle hypoactivity can also be used for imposing hyperactivity of a postural nature, inducing muscle transformations towards a slower twitch muscle.     

Effects of phosphorylation of troponin I and C protein on isometric tension and velocity of unloaded shortening in skinned single cardiac myocytes from rats

Effects on isometric tension generation and maximum velocity of unloaded shortening after exposure to cAMP-dependent protein kinase (PKA) were investigated in rat enzymatically isolated, tritonized ventricular myocytes. Exposure of myocytes to PKA in the presence of [32P]ATP resulted in phosphorylation of troponin I and C protein. Ca2+ sensitivity of isometric tension was assessed as pCa50, ie, the [Ca2+] at which tension was 50% of maximum, and was lower after PKA treatment (pCa50 5.58) than before PKA treatment (pCa50 5.74). This suggests beta-adrenergic stimulation of the heart and subsequent increases in PKA activity and phosphorylation of troponin I and C protein lead to a significant decrease in tension-generating ability at a given submaximum [Ca2+]. Unloaded shortening velocity was determined by measuring the time required to take up various amounts of slack imposed at one end of the cardiac myocyte preparation. Unloaded shortening velocity during maximum activation was 2.88 +/- 0.11 muscle lengths per second (mean +/- SEM) before PKA exposure and 2.86 +/- 0.13 muscle lengths per second after PKA exposure. Unloaded shortening velocity during 40% of maximum activation was 1.91 +/- 0.25 muscle lengths per second before PKA exposure and 2.17 +/- 0.15 muscle lengths per second after PKA exposure. The absence of an effect of PKA on unloaded shortening velocity in skinned ventricular myocytes suggests that beta-adrenergic stimulation of myocardium either does not affect myofilament velocity of shortening or alters velocity of shortening by a non-PKA-dependent process.     

Regulation of force and shortening velocity by calcium and myosin phosphorylation in chemically skinned smooth muscle

The phosphatase inhibitor okadaic acid (OA) was used to study the relationship between [Ca2+], rates of phosphorylation/dephosphorylation and the mechanical properties of smooth muscle fibres. Force/velocity relationships were determined with the isotonic quick release technique in chemically skinned guinea-pig taenia coli muscles at 22 degrees C. In the maximally thiophosphorylated muscle neither OA (10 microM) nor Ca2+ (increase from pCa 9.0 to pCa 4.5) influenced the force-velocity relationship. When the degree of activation was altered by varying [Ca2+] in the presence of 0.5 microM calmodulin, both force and the maximal shortening velocity (Vmax) were altered. At pCa 5.75, at which force was about 35% of the maximal at pCa 4.5, Vmax was 55% of the maximal value. When OA was introduced into fibres at pCa 6.0, force was increased from less than 5% to 100% of the maximal force obtained in pCa 4.5. The relationship between the degree of myosin light chain phosphorylation and force was similar in the two types of activation; varied [OA] at constant [Ca2+] and at varied [Ca2+]. The relation between force and Vmax when the degree of activation was altered with OA was almost identical to that obtained with varied [Ca2+]. The results show that Ca2+ and OA do not influence force or Vmax in the maximally phosphorylated state and suggest that the level of myosin light chain phosphorylation is the major factor determining Vmax. The finding that the relationship between force and Vmax was similar when activation was altered with OA and Ca2+ suggests, however, that alterations in the absolute rates of phosphorylation and dephosphorylation at a constant phosphorylation level do not influence the mechanical properties of the skinned smooth muscle fibres.     

Plasma lactate accumulation and distance running performance. 1979

Laboratory and field assessments were made on eighteen male distance runners. Performance data were obtained for distances of 3.2, 9.7, 15, 19.3 km (n = 18) and the marathon (n = 13). Muscle fiber composition expressed as percent of slow twitch fibers (%ST), maximal oxygen consumption (VO2max), running economy (VO2 for a treadmill velocity of 268 m/min), and the VO2 and treadmill velocity corresponding to the onset of plasma lactate accumulation (OPLA) were determined for each subject. %ST (R > or equal to .47), VO2max (r > or equal to .83), running economy (r > or equal to .49), VO2 in ml/kg min corresponding to the OPLA (r > or equal to .91) and the treadmill velocity corresponding to OPLA (r > or equal to .91) were significantly (p < .05) related to performance at all distances. Multiple regression analysis showed that the treadmill velocity corresponding to the OPLA was most closely related to performance and the addition of other factors did not significantly raise the multiple R values suggesting that these other variables may interact with the purpose of keeping plasma lactates low during distance races. The slowest and fastest marathoners ran their marathons 7 and 3 m/min faster than their treadmill velocities corresponding to their OPLA which indicates that this relationship is independent of the competitive level of the runner. Runners appear to set a race pace which allows the utilization of the largest possible VO2 which just avoids the exponential rise in plasma lactate.     

Muscle function during brief maximal exercise: accurate measurements on a friction-loaded cycle ergometer

A friction loaded cycle ergometer was instrumented with a strain gauge and an incremental encoder to obtain accurate measurement of human mechanical work output during the acceleration phase of a cycling sprint. This device was used to characterise muscle function in a group of 15 well-trained male subjects, asked to perform six short maximal sprints on the cycle against a constant friction load. Friction loads were successively set at 0.25, 0.35, 0.45, 0.55, 0.65 and 0.75 N.kg-1 body mass. Since the sprints were performed from a standing start, and since the acceleration was not restricted, the greatest attention was paid to the measurement of the acceleration balancing load due to flywheel inertia. Instantaneous pedalling velocity (v) and power output (P) were calculated each 5 ms and then averaged over each downstroke period so that each pedal downstroke provided a combination of v, force and P. Since an 8-s acceleration phase was composed of about 21 to 34 pedal downstrokes, this many v-P combinations were obtained amounting to 137-180 v-P combinations for all six friction loads in one individual, over the widest functional range of pedalling velocities (17-214 rpm). Thus, the individual's muscle function was characterised by the v-P relationships obtained during the six acceleration phases of the six sprints. An important finding of the present study was a strong linear relationship between individual optimal velocity (vopt) and individual maximal power output (Pmax) (n = 15, r = 0.95, P < 0.001) which has never been observed before. Since vopt has been demonstrated to be related to human fibre type composition both vopt, Pmax and their inter-relationship could represent a major feature in characterising muscle function in maximal unrestricted exercise. It is suggested that the present method is well suited to such analyses.     

Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse

The mechanical properties and the myosin isoform composition were studied in three isolated muscles (EDL, soleus, diaphragm) of mutant mice lacking both dystrophin and utrophin (dko). They were compared with the corresponding muscles of the normal and the dystrophin-deficient (mdx) and the utrophin-deficient (uko) mice. In comparison with mdx muscles, dko muscles show a significant reduction of the normalized isometric force, confirmed by the reduced muscular activity of the whole animal. Kinetics parameters (twitch time-to-peak and half-relaxation time) were slightly reduced, and the maximal speed of shortening of soleus, Vmax, was reduced by 30%. The maximal power output (muW/mm3) was reduced by 50% in dko soleus. In the three muscles studied, the relative myosin heavy chains (MHC) composition showed a shift towards slower isoforms. dko EDL presented a dramatic decrease of the resistance ot tetanic contraction with forced lengthenings (eccentric contractions), while muscle lacking only utrophin (uko mutants) display a normal resistance to this exacting mechanical challenge. These experiments suggest that lack of both dystrophin and utrophin is very detrimental to the mice and that mechanical properties of the muscles may explain the overall phenotype. Moreover these results bring some support to the idea that the expression of utrophin in mdx muscle compensates, to some extent, for the lack of dystrophin.     

Adrenoceptor and cholinoceptor mediated effects in the isolated urethra of cat and guinea-pig

1. Preparations of isolated bladder-urethral junction from cats and guinea-pigs were suspended in Krebs solution (37 degrees C) which was bubbled with carbogen. The urethral lumen was perfused at a very low rate (1-3 ml/h) with Krebs solution. Resistance to flow and changes in longitudinal tension (initial setting 0-5 g) were recorded. In additional experiments, tension changes in urethral circular muscle preparations were registered. 2. The urethral preparations had a basal resistance to flow within the range 5-20 cm H2O. They had a spontaneous contractile activity that was unaffected by atropine 0-1 mug/ml, phenoxybenzamine 0-1 mug/ml, and tetrodotoxin 0-1-0-5 mug/ml, suggesting it was of myogenic origin. 3. The basal characteristics and the drug-induced changes in the perfused urethras were independent of whether the longitudinal tension was recorded isometrically or isotonically, or whether the perfusion was made retrograde or antegrade. Passive changes in longitudinal tension between 0-5 and 2-0 g did not affect the resistance to flow through the urethra. 4. Adrenaline and noradrenaline, 0-01-1 mug/ml, increased longitudinal tension and resistance to flow in the perfused preparations. The effects, which were sustained and concentration-related, were blocked or reversed into inhibition in the presence of phenoxybenzamine, 0-1 mug/ml. This finding suggests that the stimulatory effects were mediated via alpha-receptors. 5. Isoprenaline, 0-001-0-005 mug/ml, relaxed and inhibited the activity in the cat urethral smooth muscle and decreased the resistance to flow both under basal conditions and when the urethra was contracted by noradrenaline or acetylcholine. The inhibitory effects were blocked by propranolol, 0-1 mug/ml, suggesting that they were mediated via beta-receptors. In guinea-pig preparations, no effect of isoprenaline was observed. 6. Acetylcholine, 0-02-0-5 mug/ml, increased the longitudinal tension and the resistance to flow through the urethras. The latter effect was less pronounced than that produced by noradrenaline, especially in the guinea-pig preparations. Noradrenaline was also more effective than ecetylcholine in contracting the circular muscle of the urethra. The effect of acetylcholine was blocked by atropine, 0-1 mug/ml, suggesting that the contractions were mediated through muscarinic cholinoceptors.