Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo.

The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated substance P-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch but had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on arteriolar diameter in the cheek pouch. On balance, these data indicate that dexamethasone attenuates grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.     

Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters

Gao, Xiao-Pei, Syed R. Akhter, and Israel Rubinstein.Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters. J. Appl.Physiol. 84(1): 169-176, 1998.The purpose ofthis study was to determine whether bradykinin mediatesovalbumin-induced increase in macromolecular efflux from the nasalmucosa of ovalbumin-sensitized hamsters in vivo and, if so, whether theL-arginine/nitric oxidebiosynthetic pathway transduces, in part, this response. We found thatsuffusion of ovalbumin onto the in situ nasal mucosa ofovalbumin-sensitized hamsters, but not of controls, elicited asignificant time- and concentration-dependent increase in clearance offluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa;P < 0.05). HOE-140, but notdes-Arg⁹,[Leu⁸]-bradykinin,andN^G-L-argininemethyl ester (L-NAME), but notN^G-D-argininemethyl ester, significantly attenuated ovalbumin-induced responses.L-Arginine, but notD-arginine, abolished the effects ofL-NAME.L-NAME also significantlyattenuated bradykinin-, but not adenosine- induced increase inmacromolecular efflux from the in situ nasal mucosa. Overall, thesedata suggest that ovalbumin increases macromolecular efflux from the insitu nasal mucosa of ovalbumin-sensitized hamsters, in part, byproducing bradykinin with subsequent activation of theL-arginine/nitric oxidebiosynthetic pathway.

     

Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs

Bonham, A. C., K. S. Kott, and J. P. Joad. Sidestreamsmoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs. J. Appl.Physiol. 81(4): 1715-1722, 1996.We determinedthe effect of sidestream tobacco smoke (SS) exposure on responses oflung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr),and arterial blood pressure (ABP) to substance P in young guinea pigs.Guinea pigs were exposed to SS or filtered air fromday 8 to days41-45 of life. They were then anesthetized andgiven three doses of intravenous substance P (1.56-4.94 nmol/kg).SS exposure augmented substance P-evoked increases in RAR activity(P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP.Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuatedsubstance P-evoked increases in RAR activity(P = 0.001) and ABP(P = 0.009) but not in peak Ptr(P = 0.06). Thus chronic exposure toSS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airwayhyperresponsiveness and cough in children chronically exposed toenvironmental tobacco smoke.

     

Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa

Gao, Xiao-pei, Hideyuki Suzuki, Christopher O. Olopade,Sergei Pakhlevaniants, and Israel Rubinstein. Purified ACE attenuates smokeless tobacco-induced increase in macromolecular effluxfrom the oral mucosa. J. Appl.Physiol. 83(1): 74-81, 1997.The purpose of thisstudy was to determine whether purified angiotensin I-converting enzyme(ACE) attenuates smokeless tobacco extract (STE)-induced increase inmacromolecular efflux from the in situ oral mucosa. Byusing intravital microscopy, we found that suffusion of an aqueousextract of smokeless tobacco elicited significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa) fromthe hamster cheek pouch (P < 0.05). Suffusion of purified rabbit lung ACEsignificantly attenuated these responses in a concentration-dependentfashion (P < 0.05). These effectswere specific because purified ACE also significantly attenuated the increase in macromolecular efflux elicited by bradykinin, which isproduced in the cheek pouch during suffusion of STE, but did notattenuate the increase elicted by adenosine. Moreover,suffusion of heat-inactivated purified ACE and purified superoxidedismutase had no significant effects on STE- andbradykinin-induced responses. Collectively, these data suggestthat exogenous ACE attenuates STE-induced increase in macromolecularefflux from the in situ oral mucosa, in part, by promoting localbradykinin catabolism.

     

Linear Relations between Carbon Dioxide Concentration and Rate of Development Towards Flowering in Sorghum, Cowpea and Soyabean

Negative linear relations were detected (P < 0·005)between the rate of progress from sowing to panicle initiationand CO₂ concentration (210-720 µmol CO₂ mol^-1 air) fortwo genotypes of sorghum [Sorghum bicolor (L.) Moench]. Relationsbetween CO₂ concentration and the rate of progress from sowingto first flowering were also negative in soyabean [Glycine max(L.) Merrill] (P < 0·025), but positive in cowpea[Vigna unguiculata (L.) Walp.] (P < 0·025), albeitthat in both grain legumes sensitivity was much less than insorghum. Thus CO₂ elevation does not delay flowering in allshort-day species. The considerable effect of CO₂ concentrationon times to panicle initiation resulted in large differencesamong the sorghum plants at this developmental stage; with increasein CO₂ concentration, plants were taller with slightly moreleaves and more pronounced apical extension. At the same timeafter sowing however, sorghum plants were heavier (P < 0·05)at 210 than at 360 µmol CO₂ mol^-1 air. In contrast, relationsbetween the dry masses of the soyabean and cowpea plants andCO₂ concentration were positive and curvilinear (P < 0·05).It is suggested that the impact of global environmental changecould be severe for sorghum production in the semi-arid tropics.Copyright1995, 1999 Academic Press Sorghum bicolor (L.) Moench., sorghum, Glycine max (L.) Merrill, soyabean, Vigna unguiculata (L.) Walp., cowpea, development, flowering, CO₂, dry matter accumulation, environmental change     

Training intensity-dependent and tissue-specific increases in lactate uptake and MCT-1 in heart and muscle

We investigatedthe effects of 3 wk of moderate- (21 m/min, 8% grade) andhighintensity treadmill training (31 m/min, 15% grade) on1) monocarboxylate transporter 1 (MCT-1) content in rat hindlimb muscles and the heart and2) lactate uptake in isolated soleus(Sol) muscles and perfused hearts. In the moderately trained groupMCT-1 was not increased in any of the muscles [Sol, extensor digitorum longus (EDL), and red (RG) and white gastrocnemius(WG)] (P > 0.05). Similarly,lactate uptake in Sol strips was also not increased(P > 0.05). In contrast, in theheart, MCT-1 (+36%, P < 0.05) andlactate uptake (+72%, P < 0.05)were increased with moderate training. In the highly trained group,MCT-1 (+70%, P < 0.05) and lactateuptake (+79%, P < 0.05) wereincreased in Sol. MCT-1 was also increased in RG (+94%,P < 0.05) but not in WG and EDL(P > 0.05). In the highly trainedgroup, heart MCT-1 (+44%, P < 0.05)and lactate uptake (+173%, P < 0.05) were increased. In conclusion, it has been shown that1) in both heart and skeletal musclelactate uptake is increased only when MCT-1 is increased; 2) training-induced increases inMCT-1 occurred at a lower training intensity in the heart than inskeletal muscle; 3) in the heart, lactate uptake was increased much more after high-intensity training than after moderate-intensity training, despite similar increases inheart MCT-1 with these two training intensities; and4) the increases in MCT-1 occurredindependently of any changes in the heart's oxidative capacity (asmeasured by citrate synthase activity).

     

Neuromuscular fatigue after maximal stretch-shortening cycle exercise

Strojnik, V., and P. V. Komi. Neuromuscular fatigueafter maximal stretch-shortening cycle exercise. J. Appl. Physiol. 84(1): 344-350, 1998.To examinesome possible sites of fatigue during short-lasting maximally intensivestretch-shortening cycle exercise, drop jumps on an inclined sledgeapparatus were analyzed. Twelve healthy volunteers performed jumpsuntil they were unable to maintain jumping height >90% of theirmaximum. After the workout, the increases in the blood lactateconcentration and serum creatine kinase activation were statisticallysignificant (P < 0.001 and P < 0.05, respectively) but rathersmall in physiological terms. The major changes after the workout wereas follows: the single twitch was characterized by smaller peak torque(P < 0.05) and shorter time to peak(P < 0.05) and half-relaxation time(P < 0.01). The double-twitch torqueremained at the same level (P > 0.05), but with a steeper maximal slope of torque rise(P < 0.05); during 20- and 100-Hzstimulation the torque declined (both P < 0.01) and the maximal voluntarytorque changed nonsignificantly but with a smaller maximal slope oftorque rise (P < 0.01) and a higheractivation level (P < 0.05),accompanied by an increased electromyogram amplitude. These findingsindicate that the muscle response after the short-lasting consecutivemaximum jumps on the sledge apparatus may involve two distinctmechanisms acting in opposite directions:1) The contractile mechanism seemsto be potentiated through a shorterCa²⁺ transient and fastercross-bridge cycling, as implied by twitch changes.2) High-frequency action potentialpropagation shows an impairment, which is suggested as the possibledominant reason for fatigue in exercise of this type.

     

Plasticity in Skeletal, Cardiac, and Smooth Muscle: Selected Contribution: IGF-I antibody prevents increases in protein synthesis in epitrochlearis muscles from refed, diabetic rats

The purpose of this study was to examine whether immune neutralizationof muscle-produced insulin-like growth factor I (IGF-I) would preventan appropriate anabolic response to refeeding in diabetic rats. MaleSprague-Dawley rats were made diabetic by partial pancreatectomy andwere randomly assigned to be either control-fed, fasted, orfasted-refed (n = 7-8 per group). Diabetes decreased rates of protein synthesis and increased rates of protein degradation in incubated epitrochlearis muscles (P < 0.05). In both groups of rats, fasting lowered protein synthesis andincreased proteolysis and subsequent refeeding returned both parameters to near basal values (P < 0.05). Neutralization ofmuscle IGF-I by the addition of IGF-I antibody to the incubation mediumreduced protein synthesis an average of 22% for all groups(P < 0.05). However, rates of protein degradation werenot affected. In nondiabetic rats, refeeding increased proteinsynthesis in both control and antibody-treated muscles(P < 0.05). Refeeding also increased protein synthesisin the control muscles from diabetic rats (P < 0.01).In contrast, muscles from diabetic rats that were incubated withanti-IGF-I did not increase protein synthesis in response to refeeding.These data suggest that immune neutralization of muscle IGF-I inhypoinsulinemic rats negated the ability of endogenous IGF-I to promoteprotein synthesis and thereby prevented an appropriate anabolic response.

     

Effect of crystalloid administration on oxygen extraction in endotoxemic pigs

We asked whethercrystalloid administration improves tissue oxygen extraction inendotoxicosis. Four groups of anesthetized pigs(n = 8/group) received either normalsaline infusion or no saline and either endotoxin or no endotoxin. Wemeasured whole body (WB) and gut oxygen delivery and consumption duringhemorrhage to determine the critical oxygen extraction ratio(ER_O2 crit). Just after onset of ischemia (critical oxygen delivery rate), gut was removed for determination of area fraction of interstitial edema and capillary hematocrit. Radiolabeled microspheres were used todetermine erythrocyte transit time for the gut. Endotoxin decreased WBER_O2 crit(0.82 ± 0.06 to 0.55 ± 0.08, P < 0.05) and gutER_O2 crit(0.77 ± 0.07 to 0.52 ± 0.06, P < 0.05). Unexpectedly, saline administration also decreased WBER_O2 crit (0.82 ± 0.06 to 0.62 ± 0.08, P < 0.05) and gutER_O2 crit (0.77 ± 0.07 to 0.67 ± 0.06, P < 0.05) in nonendotoxin pigs. Saline administration increased thearea fraction of interstitial space (P < 0.05) and resulted in arterial hemodilution(P < 0.05) but not capillaryhemodilution (P > 0.05). Salineincreased the relative dispersion of erythrocyte transit times from0.33 ± 0.08 to 0.72 ± 0.53 (P < 0.05). Thus saline administration impairs tissue oxygen extractionpossibly by increasing interstitial edema or increasing heterogeneityof microvascular erythrocyte transit times.

     

Aerosol probes of lung injury in a 28-wk longitudinal study of mild experimental emphysema in dogs

After baseline measurements of lung mechanics,effective air space diameter (EAD), and aerosol dispersion (AD), threedogs were exposed to two treatments of aerosolized papain (3 ml of a4% solution), and measurements were repeated during a 28-wk follow-upperiod. EAD and AD were measured with boluses of 0.7-µm particles ofdi-2-ethylhexl sebacate, with Pen (i.e., volumetric boluspenetration/total lung capacity) between 0.1 and 0.4. After papainexposure, EAD increased a mean of 28%(P < 0.0001) and AD (Pen = 0.3, 0.4)increased 4-7% (P < 0.03). Theprogression of injury was indicated by increasing trends in total lungcapacity (P < 0.05), residual volume(P < 0.05), and EAD(P = 0.06) through week 18. There was no evidence ofdisease progression between weeks 18 and 28, whereas some of the data forindividual dogs suggested partial recovery from lung injury atweek 28. The results show that aerosolprobes can detect and characterize mild lung injury in experimental emphysema.     

Effect of endurance training and seasonal fluctuation on coagulation and fibrinolysis in young sedentary men

Van den Burg, P. J. M., J. E. H. Hospers, M. Van Vliet, W. L. Mosterd, B. N. Bouma, and I. A. Huisveld. Effect of endurance training and seasonal fluctuation on coagulation and fibrinolysis inyoung sedentary men. J. Appl. Physiol.82(2): 613-620, 1997.The effect of 12 wk of submaximal trainingon hemostatic variables was studied in 20 young sedentary men (Tr) and19 nontraining matched controls (Con). After training, a morepronounced increase in factor VIII coagulant activity(P < 0.01), reflected in a decrease in activated partial thromboplastin time(P < 0.01) during maximal exercise,was seen. Both basal plasminogen activator inhibitor 1 antigen (PAI-1Ag) and activity (PAI-1 Act; P < 0.05), as well as basal and exercise-induced tissue-type plasminogenactivator antigen (t-PA Ag; P < 0.05), were decreased after training. The overall effect onfibrinolysis was reflected in an increase in the t-PA Act/t-PA Ag ratioin the Tr group. In contrast, during the same period (February-June),the Con group demonstrated an increase in basal PAI-1 Ag and PAI-1 Act(P < 0.05), together with anincrease in basal and exercise-induced t-PA Ag(P < 0.05). Both basal andexercise-induced t-PA Act were unchanged, but t-PA Act/t-PA Ag wasdecreased (P < 0.05) in the Congroup. We conclude that physical training promotes both coagulation andfibrinolytic potential during exercise and may reverse unfavorableseasonal effects on fibrinolysis.

     

Changes in agonist-antagonist EMG, muscle CSA, and force during strength training in middle-aged and older people

Effects of 6 mo of heavy-resistance trainingcombined with explosive exercises on neural activation of the agonistand antagonist leg extensors, muscle cross-sectional area (CSA) of thequadriceps femoris, as well as maximal and explosive strength wereexamined in 10 middle-aged men (M40; 42 ± 2 yr), 11 middle-agedwomen (W40; 39 ± 3 yr), 11 elderly men (M70; 72 ± 3 yr) and 10 elderly women (W70; 67 ± 3 yr). Maximal andexplosive strength remained unaltered during a 1-mo control period withno strength training. After the 6 mo of training, maximal isometric anddynamic leg-extension strength increased by 36 ± 4 and 22 ± 2%(P < 0.001) in M40, by 36 ± 3 and 21 ± 3% (P < 0.001) in M70,by 66 ± 9 and 34 ± 4% (P < 0.001) in W40, and by 57 ± 10 and 30 ± 3%(P < 0.001) in W70, respectively.All groups showed large increases (P < 0.05-0.001) in the maximum integrated EMGs (iEMGs) of theagonist vastus lateralis and medialis. Significant(P < 0.05-0.001) increasesoccurred in the maximal rate of isometric force productionand in a squat jump that were accompanied with increased(P < 0.05-0.01) iEMGs of theleg extensors. The iEMG of the antagonist biceps femoris muscle duringthe maximal isometric leg extension decreased in both M70 (from 24 ± 6 to 21 ± 6%; P < 0.05)and in W70 (from 31 ± 9 to 24 ± 4%;P < 0.05) to the same level asrecorded for M40 and W40. The CSA of the quadriceps femoris increasedin M40 by 5% (P < 0.05), in W40 by9% (P < 0.01), in W70 by 6%(P < 0.05), and in M70 by 2% (notsignificant). Great training-induced gains in maximal and explosivestrength in both middle-aged and elderly subjects were accompanied bylarge increases in the voluntary activation of the agonists, withsignificant reductions in the antagonist coactivation in the elderlysubjects. Because the enlargements in the muscle CSAs in bothmiddle-aged and elderly subjects were much smaller in magnitude, neuraladaptations seem to play a greater role in explaining strength andpower gains during the present strength-training protocol.

     

Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men

Ross, Robert, John Rissanen, Heather Pedwell, JenniferClifford, and Peter Shragge. Influence of diet and exercise onskeletal muscle and visceral adipose tissue in men. J. Appl. Physiol. 81(6): 2445-2455, 1996.Theeffects of diet only (DO) and diet combined with either aerobic (DA) orresistance (DR) exercise on subcutaneous adipose tissue (SAT), visceraladipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n = 11; DA, n = 11; DR,n = 11). All tissues were measured byusing a whole body multislice magnetic resonance imaging (MRI) model.Within each group, significant reductions were observed for bodyweight, SAT, and VAT (P < 0.05). Thereductions in body weight (~10%) and SAT (~25%) and VAT volume (~35%) were not different between groups(P > 0.05). For alltreatments, the relative reduction in VAT was greater than in SAT(P < 0.05). For the DA and DR groupsonly, the reduction in abdominal SAT (~27%) was greater(P < 0.05) than thatobserved for the gluteal-femoral region (~20%). Conversely, thereduction in VAT was uniform throughout the abdomen regardless oftreatment (P > 0.05). MRI-LT andMRI-SM decreased both in the upper and lower body regions for the DO group alone (P < 0.05). PeakO₂ uptake (liters) wassignificantly improved (~14%) in the DA group as was muscularstrength (~20%) in the DR group (P < 0.01). These findings indicate that DA and DR result in a greaterpreservation of MRI-SM, mobilization of SAT from the abdominal region,by comparison with the gluteal-femoral region, and improved functionalcapacity when compared with DO in obese men.

     

Effects of HCl-pepsin laryngeal instillations on upper airway patency-maintaining mechanisms

Gastroesophageal reflux has been indicated as anetiopathological factor in disorders of the upper airway. Upper airwaycollapsing pressure stimulates pressure-responsive laryngeal receptorsthat reflexly increase the activity of upper airway abductor muscles. We studied, in anesthetized dogs, the effects of repeated laryngeal instillations of HCl-pepsin (HCl-P; pH = 2) on the response of laryngeal afferent endings and the posterior cricoarytenoid muscle (PCA) to negative pressure. The effect of negative pressure on receptordischarge or PCA activity was evaluated by comparing their response toupper airway (UAO) and tracheal occlusions (TO). It is only during UAO,but not during TO, that the larynx is subjected to negative transmuralpressure. HCl-P instillation decreased the rate of discharge during UAOof the 10 laryngeal receptors studied from 56.4 ± 10.9 (SE) to 38.2 ± 9.2 impulses/s (P < 0.05). With UAO, the peak PCA moving time average, normalized by dividing itby the peak values of esophageal pressure, decreased after six HCl-Ptrials from 4.29 ± 0.31 to 2.23 ± 0.18 (n = 6;P < 0.05). The responses to TO ofeither receptors or PCA remained unaltered. We conclude that exposureof the laryngeal mucosa to HCl-P solutions, as it may occur withgastroesophageal reflux, impairs the patency-maintaining mechanismsprovided by laryngeal sensory feedback. Inflammatory and necroticalterations of the laryngeal mucosa are likely responsible for theseeffects.

     

Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans

Jungersten, Lennart, Anneli Ambring, Björn Wall, andÅke Wennmalm. Both physical fitness and acute exerciseregulate nitric oxide formation in healthy humans. J. Appl. Physiol. 82(3): 760-764, 1997.We analyzednitrate, a major stable end product of nitric oxide (NO) metabolism invivo in plasma and urine from groups of healthy subjects with differentworking capacities. Resting plasma nitrate was higher in athleticsubjects than in nonathletic controls [45 ± 2 vs. 34 ± 2 (SE) µM; P < 0.01]. In other subjects, both the resting plasma nitrate level(r = 0.53; P < 0.01) and the urinary excretionof nitrate at rest (r = 0.46; P < 0.01) correlated to thesubjects' peak work rates, as determined by bicycle ergometry. Twohours of physical exercise elevated plasma nitrate by 18 ± 4 (P < 0.01) and 16 ± 6%(P < 0.01), respectively, in athletes and nonathletes, compared with resting nitrate before exercise. We conclude that physical fitness and formation of NO at restare positively linked to each other. Furthermore, a single session ofexercise elicits an acute elevation of NO formation. The observedpositive relation between physical exercise and NO formation may helpto explain the beneficial effects of physical exercise oncardiovascular health.

     

Nitric oxide regulates oxygen uptake and hydrogen peroxide release by the isolated beating rat heart

Isolated rat heart perfused with 1.5-7.5µM NO solutions or bradykinin, which activates endothelial NOsynthase, showed a dose-dependent decrease in myocardial O₂uptake from 3.2 ± 0.3 to 1.6 ± 0.1 (7.5 µM NO, n = 18,P < 0.05) and to 1.2 ± 0.1 µM O₂ · min¹ · gtissue¹ (10 µM bradykinin, n = 10,P < 0.05). Perfused NO concentrations correlated with aninduced release of hydrogen peroxide (H₂O₂) inthe effluent (r = 0.99, P < 0.01). NO markedlydecreased the O₂ uptake of isolated rat heart mitochondria(50% inhibition at 0.4 µM NO, r = 0.99,P < 0.001). Cytochrome spectra in NO-treated submitochondrial particles showed a double inhibition of electron transfer at cytochrome oxidase and between cytochrome b andcytochrome c, which accounts for the effects in O₂uptake and H₂O₂ release. Most NO was bound tomyoglobin; this fact is consistent with NO steady-state concentrationsof 0.1-0.3 µM, which affect mitochondria. In the intact heart,finely adjusted NO concentrations regulate mitochondrial O₂uptake and superoxide anion production (reflected byH₂O₂), which in turn contributes to thephysiological clearance of NO through peroxynitrite formation.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Influence of voluntary exercise on hypothalamic norepinephrine

We combined hypothalamic tissue and plasma determinations ofnorepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol withmeasurements of abdominal fat in voluntary running rats to examine therelationship among exercise training, hypothalamic and sympatheticnervous function, and body fat stores. The hypothalamic concentrationsof norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycolwere reduced after exercise training(P < 0.01), with the amount ofnorepinephrine being strongly associated with the plasma norepinephrine(r = 0.58, P < 0.05) and dihydroxyphenylglycol (r = 0.65, P = 0.01) concentrations. Exercisetraining resulted in a diminution in abdominal fat mass(P < 0.01). A strongrelationship existed between fat mass and hypothalamic norepinephrinecontent (r = 0.83, P < 0.001). The presence of apositive relationship between the arterial and hypothalamicnorepinephrine levels provides presumptive evidence of an associationbetween noradrenergic neuronal activity of the hypothalamus andsympathetic nervous function. The observation that abdominal fat massis linked with norepinephrine in the hypothalamus raises thepossibility that alterations in body fat stores provide an afferentsignal linking hypothalamic function and the activity of thesympathetic nervous system.

     

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure

To elucidate thetime course of sympathovagal balance and its relationship to leftventricular function in heart failure, we serially evaluated leftventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined adynamic map of sympathetic and parasympathetic modulation by powerspectral analysis of heart rate variability. The left ventricular peak+dP/dt substantially fell from 3,364 ± 338 to 1,959 ± 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 ± 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the timeconstant of left ventricular pressure decay and end-diastolic pressureincreased gradually from 25 ± 4 to 47 ± 5 ms(P < 0.05) and from 10 ± 2 to21 ± 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component(0.15-1.0 Hz), a marker of parasympathetic modulation, decreasedfrom 1,928 ± 1,914 to 62 ± 68 × 10³ms²(P < 0.05) on the third day andfurther to 9 ± 12 × 10³ms²(P < 0.05) at 2 wk. Similar to thetime course of left ventricular diastolic dysfunction, plasmanorepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- tohigh-frequency component increased progressively from 135 ± 50 to 532 ± 186 pg/ml (P < 0.05) and from 0.06 ± 0.06 to 1.12 ± 1.01 (P < 0.05), respectively, at 2 wk ofpacing. These cardiac and autonomic dysfunctions recovered graduallytoward the normal values at 2 wk after cessation of pacing. Thus aparallel decline in left ventricular contractility with parasympatheticinfluence and a parallel progression in left ventricular diastolicdysfunction with sympathoexcitation suggest a close relationshipbetween cardiac dysfunction and autonomic dysregulation duringdevelopment of heart failure.

     

Bed rest decreases mechanically induced myofiber wounding and consequent wound-mediated FGF release

Using a terrestrial model of spaceflight (i.e., bed rest), weinvestigated the amount of myofiber wounding and fibroblast growthfactor (FGF) release that occurs during unloading.Myofiber wounding was determined by serum levels of the creatine kinase MM (CKMM) isoform before and after bed rest. Serum levels of both acidic FGF (aFGF) and basic FGF were also determined. A second group ofsubjects was treated in an identical fashion except that they underwenta resistive exercise program during bed rest. Bed rest alone causedsignificant (P < 0.05;n = 7) reductions in post-bed-restserum levels of both CKMM and aFGF, which were paralleled by asignificant (P < 0.05;n = 7) decrease in myofiber size. Incontrast, bed rest plus resistive exercise resulted in significant (P < 0.05;n = 7) increases in post-bed-restserum levels of both CKMM and aFGF, which were paralleled by inhibitionof the atrophic response. These results suggest that mechanicallyinduced, myofiber wound-mediated FGF release may play an important rolein the etiology of unloading-induced skeletal muscle atrophy.