Role for anions in pulmonary endothelial permeability

Griffin, M. Pamela. Role for anions in pulmonaryendothelial permeability. J. Appl.Physiol. 83(2): 615-622, 1997.-Adrenergic stimulation reduces albumin permeation across pulmonary artery endothelial monolayers and induces changes in cell morphology that aremediated by Cl flux. Wetested the hypothesis that anion-mediated changes in endothelial cellsresult in changes in endothelial permeability. We measured permeationof radiolabeled albumin across bovine pulmonary arterial endothelialmonolayers when the extracellular anion was Cl,Br,I,F, acetate(Ac), gluconate(G), and propionate(Pr). Permeability toalbumin (P_albumin)was calculated before and after addition of 0.2 mM of thephosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), whichreduces permeability. InCl, theP_albumin was 3.05 ± 0.86 × 10⁶ cm/s andfell by 70% with the addition of IBMX. The initialP_albumin was lowest forPr andAc. InitialP_albumin was higher inBr,I,G, andF than inCl. A permeability ratiowas calculated to examine the IBMX effect. The greatest IBMX effect wasseen when Cl was theextracellular anion, and the order among halide anions wasCl > Br > I > F. Although the level ofextracellular Ca²⁺ concentration([Ca²⁺]_o)varied over a wide range in the anion solutions,[Ca²⁺]_odid not systematically affect endothelial permeability in this system.When Cl was theextracellular anion, varying[Ca²⁺]_ofrom 0.2 to 2.8 mM caused a change in initialP_albumin but no changein the IBMX effect. The anion channel blockers4-acetamido-4-isothiocyanotostilbene-2,2-disulfonic acid(0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initialP_albumin and the IBMXeffect. The anion transport blockers bumetanide (0.2 mM) and furosemide(1 mM) had no such effects. We conclude that extracellular anionsinfluence bovine pulmonary arterial endothelial permeability and thatthe pharmacological profile fits better with the activity of anionchannels than with other anion transport processes.

     

Effects of hyperthermia on contraction and dilatation of rabbit femoral arteries

To analyze the effect of hyperthermia on thevascular response, the isometric response of isolated rabbit femoralartery segments was recorded at 37°C and hyperthermia (41 and44°C). Contraction to potassium (5 × 10³-5 × 10² M) was significantlygreater at 41 and 44 than at 37°C and increased by inhibition ofnitric oxide (NO) synthesis withN-nitro-L-arginine(L-NNA;10⁴ M) or endotheliumremoval at 37°C but not at 41 or 44°C. Norepinephrine (10⁹-10⁴M) produced a concentration-dependent contraction greater at 41 or 44 than at 37°C and not modified by endothelium removal orL-NNA at either temperature.Phenylephrine(10⁹-10⁴M) produced a contraction increased by warming to 44°C but not to41°C. The specific₂-adrenoceptor agonist BHT-920produced a weak contraction, reduced by the₁-adrenoceptor antagonist prazosin (10⁶ M) andincreased at 44°C but not at 41°C. The concentration-dependent contraction to endothelin-1 (ET-1;10¹¹-10⁷M) was increased by warming to 41 and 44°C and by endothelium removal or L-NNA at 37°C butnot at 41 or 44°C. Response to ET-1 was reduced by endothelinET_A-receptor antagonist BQ-123(10⁵ M) andET_B-receptor antagonist BQ-788(10⁵ M). In arteriesprecontracted with ET-1(10⁸-3 × 10⁸ M), relaxation tosodium nitroprusside(10⁸-10⁴M) was increased at 41 and 44°C vs. at 37°C, but that of ACh (10⁸-10⁴M) or adenosine(10⁸-10⁴M) was not different at all temperatures studied. Relaxation to ACh,but not adenosine, was reduced similarly byL-NNA at all temperaturesstudied. These results suggest hyperthermia in muscular arteries mayinhibit production of, and increase dilatation to, NO, resulting inunchanged relaxation to ACh and increased constriction to KCl and ET-1,and may increase constriction to stimulation of₁-adrenoceptors byNO-independent mechanisms.

     

Importance of the lactate anion in control of breathing

Hardarson, Thorir, Jon O. Skarphedinsson, and TorarinnSveinsson. Importance of the lactate anion in control ofbreathing. J. Appl. Physiol. 84(2):411-416, 1998.The purpose of this study was to examine theeffects of raising the arterialLa andK⁺ levels on minute ventilation(E) in rats. EitherLa or KCl solutions wereinfused in anesthetized spontaneously breathing Wistar rats to raisethe respective ion arterial concentration ([La] and[K⁺]) gradually tolevels similar to those observed during strenuous exercise.E, blood pressure, and heart rate wererecorded continuously, and arterial[La],[K⁺], pH, and bloodgases were repeatedly measured from blood samples. To prevent changesin pH during the Lainfusions, a solution of sodium lactate and lactic acid was used. Raising [La] to13.2 ± 0.6 (SE) mM induced a 47.0 ± 4.0% increase inE without any concomitant changes ineither pH or PCO₂. Raising[K⁺] to 7.8 ± 0.11 mM resulted in a 20.3 ± 5.28% increase inE without changes in pH. Thus ourresults show that Laitself, apart from lactic acidosis, may be important in increasing E during strenuous exercise, and weconfirm earlier results regarding the role of arterial[K⁺] in the control ofE during exercise.

     

Rat hindlimb muscle blood flow during level and downhill locomotion

Duringeccentrically biased exercise (e.g., downhill locomotion), whole bodyoxygen consumption and blood lactate concentrations are lower thanduring level locomotion. These general systemic measurements indicatethat muscle metabolism is lower during downhill exercise. This studywas designed to test the hypothesis that hindlimb muscle blood flow iscorrespondingly lower during downhill vs. level exercise. Muscle bloodflow (determined by using radioactive microspheres) was measured inrats after 15 min of treadmill exercise at 15 m/min on the level (L,0°) or downhill (D, 17°). Blood flow to ankle extensormuscles was either lower (e.g., white gastrocnemius muscle: D, 9 ± 2; L, 15 ± 1 ml · min¹ · 100 g¹) or not different(e.g., soleus muscle: D, 250 ± 35; L, 230 ± 21 ml · min¹ · 100 g¹) in downhill vs. levelexercise. In contrast, blood flow to ankle flexor muscles was higher(e.g., extensor digitorum longus muscle: D, 53 ± 5; L, 31 ± 6 ml · min¹ · 100 g¹) during downhill vs.level exercise. When individual extensor and flexor muscle flows weresummed, total flow to the leg was lower during downhill exercise (D,3.24 ± 0.08; L, 3.47 ± 0.05 ml/min). These data indicate thatmuscle blood flow and metabolism are lower during eccentrically biasedexercise but are not uniformly reduced in all active muscles; i.e.,flows are equivalent in several ankle extensor muscles and higher inankle flexor muscles.     

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow

The purpose ofthis study was to examine the bioenergetics and regulation ofO₂ uptake(O₂) and force productionin contracting muscle when blood flow was moderately reduced during asteady-state contractile period. Canine gastrocnemius muscle(n = 5) was isolated, and 3-minstimulation periods of isometric, tetanic contractions were elicitedsequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz)immediately followed by a reduction of blood flow [ischemic (I)condition] to 46 ± 3% of the value obtained at 0.5 Hz with normal blood flow. TheO₂ of thecontracting muscle was significantly (P < 0.05) reduced during the Icondition [6.5 ± 0.8 (SE) ml · 100 g¹ · min¹]compared with the same stimulation frequency with normal flow (11.2 ± 1.5 ml · 100 g¹ · min¹),as was the tension-time index (79 ± 12 vs. 123 ± 22 N · g¹ · min¹,respectively). The ratio ofO₂ to tension-time indexremained constant throughout all contraction periods. Musclephosphocreatine concentration, ATP concentration, and lactate effluxwere not significantly different during the I condition compared withthe 0.5-Hz condition with normal blood flow. However, at comparable rates of O₂ andtension-time index, muscle phosphocreatine concentration and ATPconcentration were significantly less during the I condition comparedwith normal-flow conditions. These results demonstrate that, in thishighly oxidative muscle, the normal balance ofO₂ supply to force output wasmaintained during moderate ischemia by downregulation of forceproduction. In addition,1) the minimal disruption inintracellular homeostasis after the initiation of ischemia waslikely a result of steady-state metabolic conditions having alreadybeen activated, and 2) thedifference in intracellular conditions at comparable rates ofO₂ and tension-time index between the normal flow and I condition may have been due to altered intracellular O₂ tension.

     

Training improves endothelium-dependent vasodilation in resistance vessels of patients with heart failure

Katz, Stuart D., Jeannette Yuen, Rachel Bijou, and ThierryH. LeJemtel. Training improves endothelium-dependent vasodilation in resistance vessels of patients with heart failure.J. Appl. Physiol. 82(5):1488-1492, 1997.The effects of physical training onendothelium-dependent vasodilation in skeletal muscle resistance vessels were investigated in patients with heart failure. Forearm bloodflows(ml · min¹ · 100 ml¹) in response tobrachial arterial administration of acetylcholine (5 × 10⁵ and 5 × 10⁴ M at 1 ml/min) andnitroglycerin (5 × 10⁶ and 5 × 10⁵ M at 1 ml/min) weredetermined by strain-gauge venous occlusion plethysmography before andafter 8 wk of daily handgrip exercise in 12 patients with chronic heartfailure. After 8 wk of daily handgrip exercise, the vasodilatoryresponses to acetylcholine significantly increased from pretrainingvalues, i.e., 16.6 ± 2.0 vs. 8.6 ± 1.3 ml · min¹ · 100 ml¹(P < 0.05) and 27.5 ± 1.5 vs. 14.6 ± 1.7 ml · min¹ · 100 ml¹(P < 0.05), respect- ively,whereas the vasodilatory responses to nitroglycerin did notchange. Handgrip exercise training appears to specificallyenhance endothelium-dependent vasodilation in the forearm skeletalmuscle circulation of patients with heart failure.

     

Distribution of TmDOTP5- in rat tissues: TmDOTP5- vs. CoEDTA- as markers of extracellular tissue space

The distributionof TmDOTP⁵ in rat tissuewas compared with CoEDTA,an anionic complex previously used as a marker of extracellular space.Heart, liver, muscle, blood, and urine were collected from rats afterinfusion of either complex and were quantitatively analyzed by atomicabsorption spectroscopy. Although totalTmDOTP⁵ in blood and tissuewas consistently lower (0.88 ± 0.04;n = 6) thanCoEDTA after an identicalinfusion protocol (presumably because of some association of thephosphonate complex with bone), a comparison of blood and tissuecontents indicated that the two anionic complexes distributed intoidentical extracellular spaces. Relative extracellular space in the invivo liver, as determined byTmDOTP⁵ andCoEDTA, was 0.18 ± 0.02 and 0.15 ± 0.01, respectively. The corresponding relativeextracellular space values for the in vivo heart reported by the twoagents were identical (0.11 ± 0.02). Experiments were alsoperformed to evaluate the washout kinetics ofTmDOTP⁵ from anesthesizedrats. In rats given a total dose of 0.16 mmol TmDOTP⁵, 81% appeared inurine by 180 min, <2% was found in all remaining soft tissue,leaving ~18% undetected. The rate of Tm appearance in urine was fitto a standard pharmacokinetic model that included four tissuecompartments: plasma, one fast equilbrating space, one slowequilibrating space, and one very slow equilibrating space (presumablybone). The best fit result suggests that the highly chargedTmDOTP⁵ complex is clearedfrom plasma more rapidly than is the typical lower charged Gd-basedcontrast agents and that release from bone is slow compared with renal clearance.

     

Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women

Tanaka, Hirofumi, Christopher A. DeSouza, Pamela P. Jones,Edith T. Stevenson, Kevin P. Davy, and Douglas R. Seals. Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women. J. Appl.Physiol. 83(6): 1947-1953, 1997.Using ameta-analytic approach, we recently reported that the rate of declinein maximal oxygen uptake(O_{2 max}) with age inhealthy women is greatest in the most physically active and smallest inthe least active when expressed in milliliters per kilogram per minuteper decade. We tested this hypothesis prospectively underwell-controlled laboratory conditions by studying 156 healthy, nonobesewomen (age 20-75 yr): 84 endurance-trained runners (ET) and 72 sedentary subjects (S). ET were matched across the age range forage-adjusted 10-km running performance. Body mass was positivelyrelated with age in S but not in ET. Fat-free mass was not differentwith age in ET or S. Maximal respiratory exchange ratio and rating ofperceived exertion were similar across age in ET and S, suggestingequivalent voluntary maximal efforts. There was a significant butmodest decline in running mileage, frequency, and speed with advancingage in ET.O_{2 max}(ml · kg¹ · min¹)was inversely related to age (P < 0.001) in ET (r = 0.82) and S(r = 0.71) and was higher atany age in ET. Consistent with our meta-analysic findings,the absolute rate of decline inO_{2 max} was greater inET (5.7ml · kg¹ · min¹ · decade¹)compared with S (3.2 ml · kg¹ · min¹ · decade¹;P < 0.01), but the relative (%)rate of decline was similar (9.7 vs 9.1%/decade; notsignificant). The greater absolute rate of decline inO_{2 max} in ET comparedwith S was not associated with a greater rate of decline in maximalheart rate (5.6 vs. 6.2beats · min¹ · decade¹),nor was it related to training factors. The present cross-sectional findings provide additional evidence that the absolute, but not therelative, rate of decline in maximal aerobic capacity with age may begreater in highly physically active women compared with theirsedentary healthy peers. This difference does not appear to be relatedto age-associated changes in maximal heart rate, bodycomposition, or training factors.

     

Age-related declines in maximal aerobic capacity in regularly exercising vs. sedentary women: a meta-analysis

Fitzgerald, Margaret D., Hirofumi Tanaka, Zung V. Tran, andDouglas R. Seals. Age-related declines in maximal aerobic capacityin regularly exercising vs. sedentary women: a meta-analysis. J. Appl. Physiol. 83(1): 160-165, 1997.Our purpose was to determine the relationship between habitualaerobic exercise status and the rate of decline in maximal aerobiccapacity across the adult age range in women. A meta-analytic approachwas used in which mean maximal oxygen consumption(O_{2 max}) values fromfemale subject groups (ages 18-89 yr) were obtained from thepublished literature. A total of 239 subject groups from 109 studiesinvolving 4,884 subjects met the inclusion criteria and werearbitrarily separated into sedentary (groups = 107; subjects = 2,256),active (groups = 69; subjects = 1,717), and endurance-trained (groups = 63; subjects = 911) populations.O_{2 max} averaged 29.7 ± 7.8, 38.7 ± 9.2, and 52.0 ± 10.5 ml · kg¹ · min¹,respectively, and was inversely related to age within each population (r = 0.82 to 0.87, allP < 0.0001). The rate of decline inO_{2 max} withincreasing subject group age was lowest in sedentary women (3.5ml · kg¹ · min¹· decade¹), greater inactive women (4.4ml · kg¹ · min¹· decade¹), andgreatest in endurance-trained women (6.2ml · kg¹ · min¹ · decade¹)(all P < 0.001 vs. each other). Whenexpressed as percent decrease from mean levels at age ~25 yr, therates of decline inO_{2 max} were similarin the three populations (10.0 to 10.9%/decade). Therewas no obvious relationship between aerobic exercise status and therate of decline in maximal heart rate with age. The results of thiscross-sectional study support the hypothesis that, in contrast to theprevailing view, the rate of decline in maximal aerobic capacity withage is greater, not smaller, in endurance-trained vs. sedentary women.The greater rate of decline inO_{2 max} in endurance-trained populations may be related to their higher values asyoung adults (baseline effect) and/or to greater age-related reductions in exercise volume; however, it does not appear to berelated to a greater rate of decline in maximal heart rate with age.

     

Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries

The purpose of the presentstudy was to test the hypothesis that gender influences exercisetraining-induced adaptations of vascular reactivity of porcine arteriesthat provide blood flow to skeletal muscle and femoral and brachialarteries. Male and female Yucatan miniature swine were exercise trainedon a motor-driven treadmill or cage confined for 16-20 wk.Contractile responses of arterial rings were evaluated in vitro bydetermining concentration-response curves for endothelin-1 (ET-1;10¹⁰ to 10⁷ M) and norepinephrine (NE;10¹⁰ to 10⁴ M). Relaxationresponses of arteries precontracted with 30 µM PGF₂were examined for endothelium-dependent agents [bradykinin (BK;10¹¹ to 10⁶ M), ACh (10¹⁰ to10⁴ M), and a Ca²⁺ ionophore, A-23187(10⁶ M)] and a endothelium-independent agent [sodiumnitroprusside (10¹⁰ to 10⁴ M)].Arteries from female pigs developed greater contractile force inresponse to ET-1 than arteries from male pigs, whereas contractileresponses to NE and KCl were similar in arteries from both genders.Femoral arteries from females exhibited greater endothelium-mediatedvasorelaxation (BK and ACh) than did those from males. In contrast,brachial arteries of males were more responsive to BK and ACh thanbrachial arteries of females. Exercise training increased ET-1-inducedcontractions in arteries from males (without endothelium) but not inarteries from females. Training had no effect on endothelium-dependentrelaxation in arteries from males but increased relaxation responses inbrachial arteries from females. We conclude that both gender andanatomic origin of the artery influence exercise training-inducedadaptations of vascular reactivity of porcine skeletal muscle conduit arteries.

     

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses

Tyler, Catherine M., Lorraine C. Golland, David L. Evans,David R. Hodgson, and Reuben J. Rose. Changes in maximum oxygenuptake during prolonged training, overtraining, and detraining inhorses. J. Appl. Physiol. 81(5):2244-2249, 1996.Thirteen standardbred horses were trained asfollows: phase 1 (endurance training, 7 wk),phase 2 (high-intensity training, 9 wk),phase 3 (overload training, 18 wk), andphase 4 (detraining, 12 wk). Inphase 3, the horses were divided intotwo groups: overload training (OLT) and control (C). The OLT groupexercised at greater intensities, frequencies, and durations than groupC. Overtraining occurred after 31 wk of training and was defined as asignificant decrease in treadmill run time in response to astandardized exercise test. In the OLT group, there was a significantdecrease in body weight (P < 0.05).From pretraining values of 117 ± 2 (SE)ml ^· kg^{1 ·} min¹,maximal O₂ uptake(O_{2 max}) increased by15% at the end of phase 1, and when signs of overtraining werefirst seen in the OLT group,O_{2 max} was 29%higher (151 ± 2 ml ^· kg^{1 ·} min¹in both C and OLT groups) than pretraining values. There was nosignificant reduction inO_{2 max} until after 6 wk detraining whenO_{2 max} was 137 ± 2 ml ^· kg^{1 ·} min¹.By 12 wk detraining, meanO_{2 max} was134 ± 2 ml ^· kg^{1 ·} min¹,still 15% above pretraining values. When overtraining developed, O_{2 max} was notdifferent between C and OLT groups, but maximal values forCO₂ production (147 vs. 159 ml ^· kg^{1 ·} min¹)and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLTgroup. Overtraining was not associated with a decrease inO_{2 max} and, afterprolonged training, decreases inO_{2 max} occurredslowly during detraining.

     

Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury

Lasnier, Joseph M., O. Douglas Wangensteen, Laura S. Schmitz, Cynthia R. Gross, and David H. Ingbar. Terbutalinestimulates alveolar fluid resorption in hyperoxic lung injury.J. Appl. Physiol. 81(4):1723-1729, 1996.Alveolar fluid resorption occurs by active epithelial sodium transport and is accelerated by terbutaline inhealthy lungs. We investigated the effect of terbutaline on the rate ofalveolar fluid resorption from rat lungs injured by hyperoxia. Ratsexposed to >95% O₂ for 60 h,sufficient to increase wet-to-dry lung weight and cause alveolar edema,were compared with air-breathing control rats. After anesthesia, theanimals breathed 100% O₂ for 10 min through a tracheostomy. Ringer solution was instilled into thealveoli, and the steady-state rate of volume resorbed at 6 cmH₂O pressure was measured via apipette attached to the tracheostomy tubing. Ringer solution in someanimals contained terbutaline(10³ M), ouabain(10³ M), or both. Normoxicanimals resorbed 49 ± 6 µl ^· kg^{1 ·} min¹;ouabain reduced this by 39%, whereas terbutaline increased the rate by75%. The effect of terbutaline was blocked by ouabain. Hyperoxicanimals absorbed 78 ± 9 µl ^· kg^{1 ·} min¹;ouabain reduced this by 44%. Terbutaline increased the rate by a meanof 39 µl ^· kg^{1 ·} min¹,similar to the absolute effect seen in the normoxic group, and this wasblocked by ouabain. Terbutaline accelerates fluid resorption from bothnormal and injured rat lungs via its effects on active sodiumtransport.

     

Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity

Skeletal muscle oxidative enzyme capacity is impaired inpatients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as aconsequence of the reduced physical activity level in these patients.To explore this issue, citrate synthase (CS) activity was measured inselected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con,n = 7) or elastase [emphysema(Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference betweengroups was found. Excised lung volume increased with emphysema (Con,1.5 ± 0.3 g; Emp, 3.0 ± 0.3 g,P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 ± 2.0; Emp, 39.2 ± 0.8 µmol · min¹ · gwet wt¹,P < 0.05) and vastus lateralis (Con,48.5 ± 1.5; Emp, 44.9 ± 0.8 µmol · min¹ · gwet wt¹,P < 0.05) but not in the plantaris(Con, 47.4 ± 3.9; Emp, 48.0 ± 2.1 µmol · min¹ · gwet wt¹,P < 0.05) muscle. In contrast, CSactivity increased in the costal (Con, 61.1 ± 1.8; Emp, 65.1 ± 1.5 µmol · min¹ · gwet wt¹,P < 0.05) and crural (Con, 58.5 ± 2.0; Emp, 65.7 ± 2.2 µmol · min¹ · gwet wt¹, P < 0.05) regions of the diaphragm. These data indicate that emphysema perse can induce decrements in the oxidative capacity of certainnonventilatory skeletal muscles that may contribute to exerciselimitations in the emphysematous patient.

     

Effects of dopamine and domperidone on ventilatory sensitivity to hypoxia after 8h of isocapnic hypoxia

Acclimatization to altitude involves an increase in the acutehypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR ataltitude may be generated by a decrease in peripheral dopaminergicactivity. The AHVR of nine subjects was determined with and without aprior period of 8 h of isocapnic hypoxia under each of threepharmacological conditions: 1)control, with no drug administered;2) dopamine (3 µg · min¹ · kg¹);and 3) domperidone (Motilin, 40 mg).AHVR increased after hypoxia (P  0.001). Dopaminedecreased (P  0.01), and domperidone increased (P  0.005) AHVR. The effect of both drugs on AHVR appearedlarger after hypoxia, an observation supported by a significantinteraction between prior hypoxia and drug in the analysis of variance(P  0.05). Although the increasedeffect of domperidone after hypoxia of 0.40 l · min¹ · %saturation¹[95% confidence interval (CI) 0.11 to 0.92 l · min¹ · %¹]did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.

     

Modulation of whole body protein metabolism, during and after exercise, by variation of dietary protein

The aim of this study was to investigate dietaryprotein-induced changes in whole body leucine turnover and oxidationand in skeletal muscle branched chain 2-oxo acid dehydrogenase (BCOADH) activity, at rest and during exercise. Postabsorptive subjects receiveda primed constant infusion ofL-[1-¹³C,¹⁵N]leucinefor 6 h, after previous consumption of a high- (HP; 1.8 g · kg¹ · day¹,n = 8) or a low-protein diet (LP; 0.7 g · kg¹ · day¹,n = 8) for 7 days. The subjects werestudied at rest for 2 h, during 2-h exercise at 60% maximum oxygenconsumption, then again for 2 h at rest. Exercise induced a doubling ofboth leucine oxidation from 20 µmol · kg¹ · h¹and BCOADH percent activation from 7% in all subjects. Leucine oxidation was greater before (+46%) and during (+40%,P < 0.05) the first hour of exercisein subjects consuming the HP rather than the LP diet, but there was noadditional change in muscle BCOADH activity. The results suggest thatleucine oxidation was increased by previous ingestion of an HP diet,attributable to an increase in leucine availability rather than to astimulation of the skeletal muscle BCOADH activity.

     

Combined heart rate and activity improve estimates of oxygen consumption and carbon dioxide production rates

Moon, Jon K., and Nancy F. Butte. Combined heart rateand activity improve estimates of oxygen consumption and carbon dioxideproduction rates. J. Appl. Physiol.81(4): 1754-1761, 1996.Oxygen consumption(O₂) andcarbon dioxide production (CO₂) rates were measuredby electronically recording heart rate (HR) and physical activity (PA).Mean daily O₂ andCO₂ measurements by HR andPA were validated in adults (n = 10 women and 10 men) with room calorimeters. Thirteen linear and nonlinear functions of HR alone and HR combined with PA were tested as models of24-h O₂ andCO₂. Mean sleepO₂ andCO₂ were similar to basalmetabolic rates and were accurately estimated from HR alone[respective mean errors were 0.2 ± 0.8 (SD) and0.4 ± 0.6%]. The range of prediction errorsfor 24-h O₂ andCO₂ was smallestfor a model that used PA to assign HR for each minute to separateactive and inactive curves(O₂, 3.3 ± 3.5%; CO₂, 4.6 ± 3%). There were no significant correlations betweenO₂ orCO₂ errors and subject age,weight, fat mass, ratio of daily to basal energy expenditure rate, orfitness. O₂,CO₂, and energy expenditurerecorded for 3 free-living days were 5.6 ± 0.9 ml ^· min^{1 ·} kg¹,4.7 ± 0.8 ml ^· min^{1 ·} kg¹,and 7.8 ± 1.6 kJ/min, respectively. Combined HR and PA measured 24-h O₂ andCO₂ with a precisionsimilar to alternative methods.

     

Effect of luteal phase elevation in core temperature on forearm blood flow during exercise

Kolka, Margaret A., and Lou A. Stephenson. Effect ofluteal phase elevation in core temperature on forearm blood flow duringexercise. J. Appl. Physiol. 82(4):1079-1083, 1997.Forearm blood flow (FBF) as an index of skinblood flow in the forearm was measured in five healthy women by venousocclusion plethysmography during leg exercise at 80% peak aerobicpower and ambient temperature of 35°C (relative humidity 22%;dew-point temperature 10°C). Resting esophagealtemperature (T_es) was 0.3 ± 0.1°C higher in the midluteal than in the early follicular phase ofthe menstrual cycle (P < 0.05).Resting FBF was not different between menstrual cycle phases. TheT_es threshold for onset of skinvasodilation was higher (37.4 ± 0.2°C) in midluteal than inearly follicular phase (37.0 ± 0.1°C; P < 0.05). The slope of the FBF toT_es relationship was not different between menstrual cycle phases (14.0 ± 4.2 ml · 100 ml¹ · min¹ · °C¹for early follicular and 16.3 ± 3.2 ml · 100 ml¹ · min¹ · °C¹for midluteal phase). Plateau FBF was higher during exercise inmidluteal (14.6 ± 2.2 ml · 100 ml¹ · min¹ · °C¹)compared with early follicular phase (10.9 ± 2.4 ml · 100 ml¹ · min¹ · °C¹;P < 0.05). The attenuation of theincrease in FBF to T_es occurred when T_es was 0.6°C higher andat higher FBF in midluteal than in early follicular experiments(P < 0.05). In summary, the FBF response is different during exercise in the two menstrual cycle phasesstudied. After the attenuation of the increase in FBF and whileT_es was still increasing, thegreater FBF in the midluteal phase may have been due to the effects ofincreased endogenous reproductive endocrines on the cutaneousvasculature.

     

Skeletal muscle mass and the reduction of VO2 max in trained older subjects

Proctor, David N., and Michael J. Joyner. Skeletalmuscle mass and the reduction ofO_{2 max} in trainedolder subjects. J. Appl. Physiol.82(5): 1411-1415, 1997.The role of skeletal muscle mass in theage-associated decline in maximalO₂ uptake (O_{2 max}) is poorlydefined because of confounding changes in muscle oxidative capacity andin body fat and the difficulty of quantifying active muscle mass duringexercise. We attempted to clarify these issues byexamining the relationship between several indexes of muscle mass, asestimated by using dual-energy X-ray absorptiometry and treadmillO_{2 max} in 32 chronically endurance-trained subjects from four groups(n = 8/group): young men(20-30 yr), older men (56-72 yr), young women(19-31 yr), and older women (51-72 yr).O_{2 max} per kilogrambody mass was 26 and 22% lower in the older men (45.9 vs. 62.0 ml · kg¹ · min¹)and older women (40.0 vs. 51.5 ml · kg¹ · min¹).These age differences were reduced to 14 and 13%, respectively, whenO_{2 max} was expressedper kilogram of appendicular muscle. When appropriately adjusted forage and gender differences in appendicular muscle mass by analysis ofcovariance, whole body O_{2 max} was 0.50 ± 0.09 l/min less (P < 0.001) in theolder subjects. This effect was similar in both genders.These findings suggest that the reducedO_{2 max} seen in highlytrained older men and women relative to their younger counterparts isdue, in part, to a reduced aerobic capacity per kilogram of activemuscle independent of age-associated changes in body composition, i.e.,replacement of muscle tissue by fat. Because skeletal muscleadaptations to endurance training can be well maintained in oldersubjects, the reduced aerobic capacity per kilogram of muscle likelyresults from age-associated reductions in maximalO₂ delivery (cardiac outputand/or muscle blood flow).

     

Smaller lungs in women affect exercise hyperpnea

We subjected 29 healthy young women (age: 27 ± 1 yr) with a wide range of fitness levels [maximal oxygenuptake (O_{2 max}): 57 ± 6 ml · kg¹ · min¹;35-70ml · kg¹ · min¹]to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age-and height-matched men. The higher maximal workload in highly fit(O_{2 max} > 57 ml · kg¹ · min¹,n = 14) vs. less-fit(O_{2 max} < 56 ml · kg¹ · min¹,n = 15) women caused a higher maximalventilation (E) with increased tidal volume (VT)and breathing frequency (f_b) atcomparable maximal VT/vitalcapacity (VC). More expiratory flow limitation (EFL; 22 ± 4% ofVT) was also observed duringheavy exercise in highly fit vs. less-fit women, causing higherend-expiratory and end-inspiratory lung volumes and greater usage oftheir maximum available ventilatory reserves.HeO₂ (79% He-21%O₂) vs. room air exercise trialswere compared (with screens added to equalize external apparatusresistance). HeO₂ increasedmaximal expiratory flow rates (20-38%) throughout the range ofVC, which significantly reduced EFL during heavy exercise. When EFL wasreduced with HeO₂, VT,f_b, andE (+16 ± 2 l/min) weresignificantly increased during maximal exercise. However, in theabsence of EFL (during room air exercise),HeO₂ had no effect onE. We conclude that smaller lungvolumes and maximal flow rates for women in general, and especiallyhighly fit women, caused increased prevalence of EFL during heavyexercise, a relative hyperinflation, an increased reliance onf_b, and a greater encroachment onthe ventilatory "reserve." Consequently,VT andE are mechanically constrained duringmaximal exercise in many fit women because the demand for highexpiratory flow rates encroaches on the airways' maximum flow-volumeenvelope.

     

Enhancement of intestinal water absorption and sodium transport by glycerol in rats

Wapnir, Raul A., Maria C. Sia, and Stanley E. Fisher.Enhancement of intestinal water absorption and sodium transport byglycerol in rats. J. Appl. Physiol.81(6): 2523-2527, 1996.Glycerol (Gly) is a hydrophilic,absorbable, and energy-rich solute that could make water absorptionmore efficient. We investigated the use of Gly in a high-energybeverage containing corn syrup (CS) by using a small intestineperfusion procedure in the rat, an approach shown earlier to providegood preclinical information. The effectiveness of several formulationswith Gly and CS was compared with commercial products and toexperimental formulas where Gly substituted for glucose (Glc). TheCS-Gly combination was more effective than preparations on the marketcontaining sucrose and Glc-fructose syrups (G-P and G-L, respectively)in maintaining a net water absorption balance in the test jejunal segment [CS-Gly = 0.021 ± 0.226, G-L = 1.516 ± 0.467, and G-P = 0.299 ± 0.106 (SE)µl ^· min^{1 ·} cm¹(P = 0.0113)] and in reducingsodium release into the lumen [CS-Gly = 133.2 ± 16.2, G-L = 226.7 ± 25.2, and G-P = 245.6 ± 23.4 nmol ^· min^{1 ·} cm¹(P = 0.0022)]. In otherpreparations, at equal CS concentrations (60 and 80 g/l, respectively),Gly clearly improved net water absorption over a comparableGlc-containing product [CS60-Gly = 0.422 ± 0.136 and CS80-Gly = 0.666 ± 0.378 vs. CS60-Glc = 0.282 ± 0.200 andCS80-Glc = 1.046 ± 0.480 µl ^· min^{1 ·} cm¹(P = 0.0019)]. On the basis ofthe data of this rat intestine perfusion model, Gly could be a usefulingredient in energy-rich beverages and might enhance fluid absorptionin humans.