Local and remote arteriolar dilations initiated by skeletal muscle contraction

To investigate the relationship between skeletal muscle metabolism and arteriolar dilations in the region local to contracting muscle fibers as well as dilations at remote arteriolar regions upstream, we used a microelectrode on cremaster muscle of anesthetized hamsters to stimulate four to five muscle fibers lying approximately perpendicular to and overlapping a transverse arteriole. Before, during, and after muscle contraction, we measured the diameter of the arteriole at the site of muscle fiber overlap (local) and at a remote site approximately 1,000 microm upstream. Two minutes of 2-, 4-, or 8-Hz stimulation (5-10 V, 0.4-ms duration) produced a significant dilation locally (8.2 +/- 2.0-, 22.5 +/- 2.4-, and 30.9 +/- 2.1-microm increase, respectively) and at the remote site (4.2 +/- 0.8, 11.0 +/- 1.1, and 18.9 +/- 2.7 microm, respectively). Muscle contraction at 4 Hz initiated a remote dilation that was unaffected by 15-min micropipette application of either 2 microM tetrodotoxin, 0.07% halothane, or 40 microM 18-beta-glycyrrhetinic acid between the local and upstream site. Therefore, at the arteriolar level, muscle contraction initiates a robust remote dilation that does not appear to be transmitted via perivascular nerves or gap junctions.     

A 31P-n.m.r. study of the acute effects of beta-blockade on the bioenergetics of skeletal muscle during contraction.

1. The effects of beta-adrenoceptor antagonist administration on skeletal muscle contractile performance and bioenergetics in vivo have been investigated during unilateral sciatic nerve stimulation in the rat. 2. Two muscle stimulation protocols have been used: supramaximal stimulation at 4 Hz, or incremental supramaximal stimulation at 1, 2 and 4 Hz. Changes in high-energy phosphate concentrations were followed using 31P-n.m.r., and gastrocnemius muscle twitch characteristics were monitored continuously. 3. Under all conditions investigated, DL-propranolol administration (2.5 mg/kg body wt.) caused a significant decrease in cyclic AMP concentrations in resting and stimulated gastrocnemius muscle, prevented an increase in heart rate upon muscle stimulation, but did not affect plasma glucose, fatty acid or lactate concentrations in comparison with values obtained in control experiments. 4. Administration of DL-propranolol 5 min or 35 min before unilateral stimulation of 4 Hz had no effect on changes in muscle phosphocreatine, ATP or Pi concentrations, intracellular pH or contractile performance. 5. In contrast, animals receiving DL-propranolol 5 min before unilateral stimulation of 1, 2 and 4 Hz showed a significant deterioration in gastrocnemius muscle tension development during 2 and 4 Hz stimulation compared with control animals. Concurrent with this change in contractile performance was a higher muscle concentration of phosphocreatine, a lower concentration of Pi and no significant change in intramuscular pH compared with control experiments. 6. The changes in muscle performance and bioenergetics observed during the incremental stimulation protocol were not observed when D-propranolol was administered and could be completely circumvented by a short period of muscle stimulation of 4 Hz prior to initiation of the incremental stimulation protocol. 7. Mechanisms are discussed which may account for the failure of gastrocnemius muscle to generate the expected force during the incremental stimulation protocol in the presence of beta-blockade.     

Rapid biphasic arteriolar dilations induced by skeletal muscle contraction are dependent on stimulation characteristics

To test the hypothesis that measurable changes in microvasculature dilation occur in response to a single short-duration tetanic contraction, we contracted three to five skeletal muscle fibres of the hamster cremaster muscle microvascular preparation (in situ) and evaluated the response of an arteriole overlapping the active muscle fibres. Arteriolar diameter (baseline diameter = 16.4 +/- 0.9 micro m, maximum diameter = 34.7 +/- 1.2 micro m) was measured before and after a single contraction resulting from a range of stimulus frequencies (4, 10, 20, 30, 40, 60, and 80 Hz) within a 250- or 500-ms train. Four and 10 Hz produced a significant dilation at 2.9 +/- 0.4 and 6.5 +/- 2.8 s, respectively, within a 250-ms train and 3.0 +/- 0.2 and 6.1 +/- 1.3 s, respectively, within a 500-ms train. Biphasic dilations were observed within a 250-ms train at 20 Hz (at 3.9 +/- 0.9 and 22.1 +/- 4.3 s), 30 Hz (at 2.7 +/- 0.3 and 17.5 +/- 2.9 s), and 40 Hz (at 3.8 +/- 0.4 and 23.2 +/- 2.6 s) and within a 500-ms train at 20 Hz (at 4.8 +/- 0.4 and 31.9 +/- 3.8 s) and 30 Hz (at 3.4 +/- 0.3 and 27.6 +/- 3.0 s). A single dilation was observed within a 250-ms train at 60 Hz (at 5.1 +/- 0.7 s) and 80 Hz (at 14.2 +/- 3.3 s) and within a 500-ms train at 40 Hz (at 9.9 +/- 3.2 s), 60 Hz (at 7.9 +/- 2.1 s), and 80 Hz (at 13.4 +/- 4.0 s). We have shown that a single contraction ranging from a single twitch (4 Hz, 250 ms) to fused tetanic contractions produces significant arteriolar dilations and that the pattern of dilation is dependent on the stimulus frequency and train duration.     

Renal microvasculature of the black bear (Ursus americanus)

This study of the Black bear (Ursus americanus) was undertaken to provide basic information related to structural modifications in the renal microvasculature that might provide insight into the drastic alteration in renal urinary output that occurs during winter sleep. Vascular casts, as well as light microscopy and scanning electron microscopy, were used to study the vascular components of the juxtaglomerular complex and related vessels. Histologically, arterial cushions were readily identified at the origin of the afferent arterioles. In the area of the juxtaglomerular complex, the wall of the afferent arteriole appeared to be highly modified. The smooth muscle cells at this site demonstrated a change in morphology and orientation, and the diameter of the arteriole was altered. The pattern of the vascular casts at the origin of the afferent arteriole varied from that portion at the glomerulus, suggesting a modification of the vascular wall near the renal corpuscle. Although the morphology of the renal microvasculature of the Black bear is similar to that of other mammals in some aspects, it is dissimilar to that of other carnivores and of the human kidney in that there are structural modifications of the afferent arteriole that may contribute to a reduction of blood flow to the nephron during winter sleep.     

Remote arteriolar dilations in response to muscle contraction under capillaries

In hamster cremaster muscle, it has been shown previously that contraction of skeletal muscle fibers underlying small groups of capillaries (modules) induces dilations that are proportional to metabolic rate in the two arteriolar generations upstream of the stimulated capillaries (Berg BR, Cohen KD, and Sarelius IH. Am J Physiol Heart Circ Physiol 272: H2693-H2700, 1997). These remote dilations were hypothesized to be transmitted via gap junctions and not perivascular nerves. In the present study, halothane (0.07%) blocked dilation in the module inflow arteriole, and dilation in the second arteriolar generation upstream, the branch arteriole, was blocked by both 600 mosM sucrose and halothane but not tetrodotoxin (2 microM). Dilations in both arterioles were not blocked by the gap junction uncoupler 18-beta-glycyrrhetinic acid (40 microM), and 80 mM KCl did not block dilation of the module inflow arteriole. These data implicate a gap junctional-mediated pathway insensitive to 18-beta-glycyrrhetinic acid in dilating the two arterioles upstream of the capillary module during "remote" muscle contraction. Dilation in the branch arteriole, but not the module inflow arteriole, was attenuated by 100 microM N(omega)-nitro-L-arginine. Thus selective contraction of muscle fibers underneath capillaries results in dilations in the upstream arterioles that have characteristics consistent with a signal that is transmitted along the vessel wall through gap junctions, i.e., a conducted vasodilation. The observed insensitivities to 18-beta-glycyrrhetinic acid, to KCl, and to N(omega)-nitro-L-arginine suggest, however, that there are multiple signaling pathways by which remote dilations can be initiated in these microvessels.     

Role of the thromboxane A2 receptor in the vasoactive response to ischemia-reperfusion injury.

Neutrophil-endothelial adhesion in venules and progressive vasoconstriction in arterioles seem to be important microcirculatory events contributing to the low flow state associated with ischemia-reperfusion injury of skeletal muscle. Although the neutrophil CD-18 adherence function has been shown to be a prerequisite to the vasoconstrictive response, the vasoactive substances involved remain unknown. The purpose of this study was to evaluate the role of thromboxane A2 receptor in the arteriole vasoactive response to ischemia-reperfusion injury. An in vivo microscopy preparation of transilluminated gracilis muscle in male Wistar rats (175 +/- 9 g) (n = 12) was used for this experiment. Three experimental groups were evaluated in this study: (1) sham, flap raised, no ischemia (20 venules, 20 arterioles), (2) 4 hours of global ischemia only (19 venules, 22 arterioles), and (3) 4 hours of global ischemia + thromboxane A2 receptor antagonist (ONO-3708) (17 venules, 20 arterioles). ONO-3708 (5 mg/kg), a specific competitive antagonist of thromboxane A2 receptor, was infused at a rate of 0.04 ml/minute into the contralateral femoral vein 30 minutes before reperfusion. Mean arterial blood pressure was not changed at this dose of ONO-3708 (88 +/- 6 mmHg before infusion, 81 +/- 4 mmHg after infusion, n = 3). The number of leukocytes rolling and adherent to endothelium (15-sec observation) were counted in 100-microm venular segments, and arteriole diameters were measured at 5, 15, 30, 60, and 120 minutes of reperfusion. Leukocyte counts and arteriole diameters were analyzed with two-way factorial analysis of variance for repeated measures and Duncan's post hoc mean comparison. Statistical significance was indicated by a p < or = 0.05. The ischemia-reperfusion-induced vasoconstriction was significantly reduced by the thromboxane A2 receptor antagonist (ONO-3708). The mean arteriole diameters at 30, 60, and 120 minutes reperfusion were significantly greater in the treated animals than in the ischemia-reperfusion controls. Despite a significant increase in treated mean arteriole diameters, 30 percent of arterioles still demonstrated vasoconstriction. Neutrophil-endothelial adherence was not reduced by ONO-3708. Thromboxane A2 receptor blockade significantly reduces but does not eliminate ischemia-reperfusion-induced vasoconstriction in this model. This finding suggests that additional and perhaps more important vasoactive mediators contribute to vasoconstriction. Furthermore, thromboxane A2 receptor blockade has no effect on polymorphonuclear endothelial adherence.     

Effect of cycle frequency and excursion amplitude on work done by rat diaphragm muscle

Strips of isolated rat diaphragm muscle were attached to a servomotor-transducer apparatus, and the muscle length was cycled in a sinusoidal fashion about the length at which maximum isometric twitch force was developed, Lo. The amplitude of the length displacement (excursion amplitude) and rate of cycling were varied between 3 and 13% Lo and 1-4 Hz respectively. The muscle was tetanically stimulated (100 Hz, supramaximal voltage, stimulus duration (duty cycle) 20% of the length cycle period) during the shortening stage of the imposed length cycle at the phase that yielded maximum net positive work. The force and displacement of the muscle were recorded. Work per cycle was calculated from the area of the loop formed by plotting force against length for one full stretch-shorten cycle. Work per cycle decreased, but power increased, as cycle frequency was increased from 1 to 4 Hz. Maximum work done per cycle was about 12.8 J/kg at a cycle frequency of 1 Hz. Maximum mean power developed was about 27 W/kg and occurred at a cycle frequency of 4 Hz. Work and power were maximum at an excursion amplitude of 13% of Lo (i.e., Lo +/- 6.5%). Measured work and power output are considerably less than values estimated from length-tension and force-velocity curves.     

The Effect of the Stimulation Regime on Palaemon serratus Tail Muscle Energy Metabolism

The evolution of phosphometabolites was determined in the abdominal muscle of a crustacean Palaemon serratus during intermittent electrical stimulation at 1, 2 and 4 Hz and during natural escape behavior.The changes in AMP, IMP, phosphomonoesters, adenylate energy charge and ATP/ADP ratio were not affected by the frequency of electrical stimulation. On the contrary, changes in ATP, ADP and sum of adenylates depended on the stimulation protocol: degradation of ATP and accumulation of ADP were not significantly different after electrical stimulation at 2 and 4 Hz as compared to manual stimulation, but differed from the 1 Hz stimulation protocol values. The sum of adenylates decreased similarly after 2 and 4 Hz stimulation and manual protocols. The different exercise protocols did not produce any changes in AMP and IMP accumulation, ATP/ADP ratio and A.E.C. After manual stimulation, the phosphomonoester and phosphoarginine concentrations were similar to the variations observed in the all electrical stimulation protocols, while the Pi levels were similar to the variations observed in the 4 Hz stimulation protocol only. The NMR index decrease was significantly higher after the manual and 4 Hz stimulation protocols.     

Net lactate uptake during progressive steady-level contractions in canine skeletal muscle

The purpose of this study was to determine the changes in net lactate uptake (L) by skeletal muscle with a constant elevated blood lactate concentration during steady-level contractions of increasing intensity. The gastrocnemius-plantaris muscle group was isolated in situ in 11 anesthetized dogs. An infusion of lactate/lactic acid at a pH of 3.5-3.7 established a blood lactate concentration of approximately 9 mM while maintaining normal blood gas/pH status. L was measured during three consecutive 30-min periods during which the muscles 1) rested, 2) contracted at 1 Hz, and 3) contracted at 4 Hz. L was always positive, indicating net uptake throughout the lactate/lactic acid infusion. Steady-level O2 uptake averaged 10.9 +/- 2.2 ml.kg-1.min-1 (0.49 +/- 0.10 mmol.kg-1.min-1) at rest, 39.3 +/- 2.1 (1.75 +/- 0.09) at 1 Hz, and 127.8 +/- 9.2 (5.70 +/- 0.41) at 4 Hz. Steady-level L increased with the metabolic rate from 0.113 +/- 0.058 mmol.kg-1.min-1 at rest to 0.329 +/- 0.026 at 1 Hz and 0.715 +/- 0.108 at 4 Hz. The increase in L from rest to 1 Hz was accomplished mainly by an increase in arteriovenous lactate difference, whereas the increase from 1 to 4 Hz was entirely due to a large increase in blood flow. These results support the idea that skeletal muscle is not simply a producer of lactate but can be a significant consumer of lactate even during contractions with a large elevation in metabolic rate.     

Comparison of the effect of ATP on intracellular calcium ion dynamics between rat testicular and cerebral arteriole smooth muscle cells

Adenosine 5'-triphosphate (ATP), when released from neuronal and non-neuronal tissues, interacts with cell surface receptors produces a broad range of physiological responses. The goal of the present study was to examine the issue of whether vascular smooth muscle cells respond to ATP. To this end, the dynamics of the intracellular concentration of calcium ions ([Ca(2+)](i)) in smooth muscle cells in testicular and cerebral arterioles was examined by laser scanning confocal microscopy. ATP produced an increase in [Ca(2+)](i) in arteriole smooth muscle cells. While P1 purinoceptor agonists had no effect on this process, P2 purinoceptor agonists induced a [Ca(2+)](i) increase and a P2 purinoceptor antagonist, suramin, completely inhibited ATP-induced [Ca(2+)](i) dynamics in both arteriole smooth muscle cells.In testicular arterioles, Ca(2+) channel blockers and the removal of extracellular Ca(2+), but not thapsigargin pretreatment, abolished the ATP-induced [Ca(2+)](i) dynamics. In contrast, Ca(2+) channel blockers and the removal of extracellular Ca(2+) did not completely inhibit ATP-induced [Ca(2+)](i) dynamics in cerebral arterioles. Uridine 5'-triphosphate caused an increase in [Ca(2+)](i) only in cerebral arterioles and alpha,beta-methylene ATP caused an increase in [Ca(2+)](i) in both testicular and cerebral arterioles.We conclude that testicular arteriole smooth muscle cells respond to extracellular ATP via P2X purinoceptors and that cerebral arteriole smooth muscle cells respond via P2X and P2Y purinoceptors.     

结缔组织生长因子在肺纤维化初期肺动脉中的表达

本研究观察了博莱霉素(bleomycin,BLM)诱导肺纤维化初期肺动脉压、肺动脉壁Ⅰ、Ⅲ型胶原的含量以及肺动脉壁结缔组织生长因子(connective tissue growth factor,CTGF)免疫阳性表达和分布.用气管内一次性滴注BLM(5 mg/kg体重)的方法复制肺纤维化动物模型大鼠;用右心漂浮导管技术检测肺动脉压;用天狼星红胶原纤维特异染色和偏振光观察肺动脉Ⅰ、Ⅲ型胶原;用免疫组织化学法检测肺动脉壁CTGF表达.结果显示:滴注BLM后第14天,大鼠肺动脉压高于对照组大鼠(P<0.05);肺动脉主干和肺内动脉壁Ⅰ、Ⅲ型胶原的染色面积大于对照组大鼠(P<0.05,P<0.01),肺动脉主干血管壁Ⅰ、Ⅲ型胶原染色面积的比值高于对照组大鼠(P<0.05);肺动脉主干和肺内动脉壁CTGF免疫染色面积均大于对照组大鼠,平均光密度也高于对照组大鼠(均P<0.05);增多的CTGF免疫阳性细胞主要分布在肺动脉的平滑肌层和内皮层.以上结果表明,在BLM致肺纤维化形成初期肺动脉高压和肺血管壁结构重塑过程中,肺动脉壁平滑肌层和内皮层CTGF表达增多,这可能是肺动脉高压维持和发展的机制之一.     

Developmental changes in neuromuscular transmission in the rat diaphragm.

Neuromuscular transmission was studied in diaphragms from rats of three ages, 4-7 days old, 11-12 days old, and adults with the use of an in vitro phrenic nerve-hemidiaphragm preparation. Each hemidiaphragm was stimulated via either muscle or nerve with 1-s stimulus trains at frequencies from 10 to 100 Hz. The patterns of force development obtained in response to the two routes of stimulation were compared for each group. Diaphragms from adults developed maximum force in response to stimulation of approximately 40 Hz with no significant decrease in force at higher frequencies. Within each stimulus train, once peak force was achieved, it was maintained for the remainder of the stimulus and responses to nerve and muscle stimulation were almost identical. In contrast, diaphragms from 4- to 7-day-old rats developed maximum force at approximately 20 Hz; stimulation at greater than or equal to 60 Hz induced significantly less peak force. This decrease in peak force at higher frequencies was significantly larger for nerve than for muscle stimulation. In addition, during each nerve stimulus train diaphragms from 4- to 7-day-old rats were unable to maintain peak force, which decreased at frequencies greater than 20 Hz. The decrease in force reached approximately 50% of peak at stimulation frequencies greater than or equal to 60 Hz. Diaphragms from 11- to 12-day-old rats showed intermediate responses. Based on the responses to phrenic nerve stimulation, we conclude that the neonatal rat diaphragm shows marked neuromuscular transmission failure that is not seen in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impedance of the chest wall during sustained respiratory muscle contraction

We measured total chest wall impedance (Zw), "pathway impedances" of the rib cage (Zrcpath), and diaphragm-abdomen (Zd-apath), and impedance of the belly wall including abdominal contents (Zbw+) in five subjects during sustained expiratory (change in average pleural pressure [Ppl] from relaxation = 10 and 20 cmH2O) and inspiratory (change in Ppl = -10 and -20 cmH2O) muscle contraction, using forced oscillatory techniques (0.5-4 Hz) we have previously reported for relaxation (J. Appl. Physiol. 66: 350-359, 1989). Chest wall configuration and mean lung volume were kept constant. Zw, Zrcpath, Zd-apath, and Zbw+ all increased greatly at each frequency during expiratory muscle contraction; increases were proportional to effort. Zw, Zrcpath, and Zd-apath increased greatly during inspiratory muscle contraction, but Zbw+ did not. Resistances and elastances calculated from each of the impedances showed the same changes during muscle contraction as the corresponding impedances. Each of the resistances decreased as frequency increased, independent of effort; elastances generally increased with frequency. These frequency dependencies were similar to those measured in relaxed or tetanized isolated muscle during sinusoidal stretching (P.M. Rack, J. Physiol. Lond. 183: 1-14, 1966). We conclude that during respiratory muscle contraction 1) chest wall impedance increases, 2) changes in regional chest wall impedances can be somewhat independent, depending on which muscles contract, and 3) increases in chest wall impedance are due, at least in part, to changes in the passive properties of the muscles themselves.     

Multiple dilator pathways in skeletal muscle contraction-induced arteriolar dilations

To determine whether nitric oxide (NO), adenosine (Ado) receptors, or ATP-sensitive potassium (K(ATP)) channels play a role in arteriolar dilations induced by muscle contraction, we used a cremaster preparation in anesthetized hamsters in which we stimulated four to five muscle fibers lying perpendicular to a transverse arteriole (maximal diameter approximately 35-65 microm). The diameter of the arteriole at the site of overlap of the stimulated muscle fibers (the local site) and at a remote site approximately 1,000 microm upstream (the upstream site) was measured before, during, and after muscle contraction. Two minutes of 4-Hz muscle stimulation (5-15 V, 0.4 ms) produced local and upstream dilations of 19 +/- 1 and 10 +/- 1 microm, respectively. N(omega)-nitro-L-arginine (10(-4) M; NO synthase inhibitor), xanthine amine congener (XAC; 10(-6) M; Ado A(1), A(2A), and A(2B) receptor antagonist), or glibenclamide (Glib; 10(-5) M; K(ATP) channel inhibitor) superfused over the preparation attenuated the local dilation (by 29.7 +/- 12.7, 61.8 +/- 9.0, and 51.9 +/- 14.9%, respectively), but only XAC and Glib attenuated the upstream dilation (by 68.9 +/- 6.8 and 89.1 +/- 6.4%, respectively). Furthermore, only Glib, when applied to the upstream site directly, attenuated the upstream dilation (48.1 +/- 9.1%). Neither XAC nor Glib applied directly to the arteriole between the local and the upstream sites had an effect on the magnitude of the upstream dilation. We conclude that NO, Ado receptors, and K(ATP) channels are involved in the local dilation initiated by contracting muscle and that both K(ATP) channels and Ado receptor stimulation, but not NO, play a role in the manifestation of the dilation at the upstream site.     

Blood-flow route from the hepatic artery and portal vein to the sinusoid in normal human liver observed by confocal laser scanning microscopy

OBJECTIVE: To observe the microvasculature in normal human liver. STUDY DESIGN: Four autopsy livers cut into 50-micron-thick sections were observed by confocal laser scanning microscopy. Immunofluorescence was performed using anti-alpha smooth muscle actin (alpha-SMA) antibody. In addition, double immunofluorescence was performed on the other sections using antilysozyme antibody. The routes from the portal vein branches and hepatic artery branches to the sinusoids were defined as follows: portal venule, septal branch, inlet venule, hepatic arteriole and terminal hepatic arteriole. RESULTS: The reactivity of the walls of septal branches and inlet venule was positive for alpha-SMA. Lysozyme-positive cells (Kupffer cells) were dense in the sinusoids but were sparse in the septal branches and absent from the inlet venules. Terminal hepatic arterioles were observed along the septal branch, and the anastomoses between them were observed at the peripheral portion. No routes opening directly from the terminal hepatic arteriole into the sinusoids or arterioportal anastomoses in the portal tract were observed on alpha-SMA-stained sections. CONCLUSION: Regulation of the microcirculation in human liver may be performed by the smooth muscle layer of both peripheral portal and hepatic arterial routes.     

Muscle O2 deficit during hypoxia and two levels of O2 demand

We have examined the relative deficits in tension development and O2 uptake in contracting skeletal muscle during severe hypoxic hypoxia. Anesthetized mongrel dogs were ventilated to maintain an end-tidal PCO2 between 35 and 40 Torr. Venous outflow from the gastrocnemius muscle was measured using an electromagnetic flow probe. The tendon was cut and attached to a strain gauge. The muscle was stimulated to contract isometrically at 2 or 4 Hz for 20 min. Hypoxia (9% O2 in N2) was then imposed for 30 min, followed by 30 min of normoxia. Blood flow first increased in proportion to the contraction frequency and then increased further a similar amount in both groups during hypoxia. O2 extraction and blood flow reached maximal levels during hypoxia in the 2-Hz group. The further O2 deficit that was accumulated during 4 Hz and hypoxia was, therefore, a result of the greater discrepancy between O2 supply and demand. O2 uptake decreased more in hypoxia than did developed tension. These results are best explained by ATP supplementation from nonaerobic energy sources that was promoted by the free-flow condition of hypoxic hypoxia.     

Reduced nitric oxide bioavailability contributes to skeletal muscle microvessel rarefaction in the metabolic syndrome

This study tested the hypothesis that chronically elevated oxidant stress contributes to impaired active hyperemia in skeletal muscle of obese Zucker rats (OZR) vs. lean Zucker rats (LZR) through progressive deteriorations in microvascular structure. Twelve-week-old LZR and OZR were given 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) in the drinking water for approximately 4 wk. Subsequently, perfusion of in situ gastrocnemius muscle was determined during incremental elevations in metabolic demand, while a contralateral skeletal muscle arteriole and the gastrocnemius muscle was removed to determine dilator reactivity, vessel wall mechanics, and microvessel density. Under control conditions, active hyperemia was impaired at all levels of metabolic demand in OZR, and this was correlated with a reduced microvessel density, increased arteriolar stiffness, and impaired dilator reactivity. Chronic tempol ingestion improved perfusion during moderate to high metabolic demand only and was associated with improved arteriolar reactivity and microvessel density; passive vessel mechanics were unaltered. Combined antioxidant therapy and nitric oxide synthase inhibition in OZR prevented much of the restored perfusion and microvessel density. In LZR, treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) hydrochloride and hydralazine (to prevent hypertension) impaired active hyperemia, dilator reactivity, and microvessel density, although arteriolar distensibility was not altered. These results suggest that with the development of the metabolic syndrome, chronic reductions in nitric oxide bioavailability, in part via the scavenging actions of oxidative free radicals, contribute to a loss of skeletal muscle microvessels, leading to impaired muscle perfusion with elevated metabolic demand.     

Effect of muscle length on electromyogram in a canine diaphragm strip preparation

The relationship between diaphragm electromyogram (EMG), isometric force, and length was studied in the canine diaphragm strip with intact blood supply and innervation under three conditions: supramaximal tetanic (100 Hz) phrenic nerve stimulation (STPS; n = 12), supramaximal phrenic stimulation at 25 Hz (n = 15), and submaximal phrenic stimulation at 25 Hz (n = 5). In the same preparation, the EMG-length relationship was also examined with direct muscle stimulation when the neuromuscular junction was blocked. EMG from three different sites and via two types of electrodes (direct or sewn-in and surface) were recorded during isometric contraction at different lengths. Direct EMGs were recorded from two bipolar electrodes sutured into the strip, one near its central end and the other near its costal end. A third EMG electrode configuration summed potentials from the whole strip by recording potentials between central and costal sites. Surface EMGs were recorded by a bipolar spring clip electrode that made contact with upper and lower surfaces of the muscle strip with light pressure. In all conditions of stimulation with different types of electrodes, all EMGs decreased significantly (P less than 0.05) when muscle length was changed from 50 to 120% of resting length (L0). Minimal and maximal force outputs were observed at 50 and 120% of L0, respectively, in all experiments. The results of this study indicated that the muscle length is a significant variable that affects the EMG recording and that the diaphragmatic EMG may not be an accurate reflection of phrenic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproducibility of the mean power frequency of the surface electromyogram

There is evidence in the literature that the decrease of mean power frequency (MPF) during exercise is greater as a muscle become more fatigued. After strenuous exercise this phenomenon can last several days. It is usually assumed, however, that the MPF has a good reproducibility. In this study the reproducibility of the MPF of the surface electromyogram of the biceps brachii muscle was investigated for five subjects on 5 successive days. Force level, muscle length and skin temperature were kept constant. The results show that interindividual differences in MPF were large (SD 11.5 Hz). However, during these 5 days, the range in MPF for individual subjects was small. The SD of the trials within subjects and days was 2.0 Hz, while the SD trials excluded). It is hypothesized that this SD may be due to variations in the electrode replacement. It is concluded that the variability in MPF for a subject is small compared to the decrease of the MPF associated with muscle fatigue and which can therefore be determined reliably during longitudinal studies.     

Venular endothelium-derived NO can affect paired arteriole: a computational model

Venular endothelial cells can release nitric oxide (NO) in response to intraluminal flow both in isolated venules and in vivo. Experimental studies suggest that venular endothelium-released NO causes dilation of the adjacent paired arteriole. In the vascular wall, NO stimulates its target hemoprotein, soluble guanylate cyclase (sGC), which relaxes smooth muscle cells. In this study, a computational model of NO transport for an arteriole and venule pair was developed to determine the importance of the venular endothelium-released NO and its transport to the adjacent arteriole in the tissue. The model predicts that the tissue NO levels are affected within a wide range of parameters, including NO-red blood cell reaction rate and NO production rate in the arteriole and venule. The results predict that changes in the venular NO production affected not only venular endothelial and smooth muscle NO concentration but also endothelial and smooth muscle NO concentration in the adjacent arteriole. This suggests that the anatomy of microvascular tissue can permit the transport of NO from arteriolar to venular side, and vice versa, and may provide a mechanism for dilation of proximal arterioles by venules. These results will have significant implications for our understanding of tissue NO levels in both physiological and pathophysiological conditions.