Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise

González-Alonso, José, RicardoMora-Rodríguez, Paul R. Below, and Edward F. Coyle.Dehydration markedly impairs cardiovascular function inhyperthermic endurance athletes during exercise. J. Appl. Physiol. 82(4): 1229-1236, 1997.Weidentified the cardiovascular stress encountered by superimposingdehydration on hyperthermia during exercise in the heat and themechanisms contributing to the dehydration-mediated stroke volume (SV)reduction. Fifteen endurance-trained cyclists [maximalO₂ consumption(O_{2 max}) = 4.5 l/min] exercised in the heat for 100-120 min and either became dehydrated by 4% body weight or remained euhydrated by drinkingfluids. Measurements were made after they continued exercise at 71%O_{2 max} for 30 minwhile 1) euhydrated with anesophageal temperature (T_es) of38.1-38.3°C (control); 2)euhydrated and hyperthermic (39.3°C);3) dehydrated and hyperthermic withskin temperature (T_sk) of34°C; 4) dehydrated withT_es of 38.1°C and T_sk of 21°C; and5) condition4 followed by restored blood volume. Compared withcontrol, hyperthermia (1°C T_esincrease) and dehydration (4% body weight loss) each separatelylowered SV 7-8% (11 ± 3 ml/beat;P < 0.05) and increased heart ratesufficiently to prevent significant declines in cardiac output.However, when dehydration was superimposed on hyperthermia, thereductions in SV were significantly (P < 0.05) greater (26 ± 3 ml/beat), and cardiac output declined 13% (2.8 ± 0.3 l/min). Furthermore, mean arterialpressure declined 5 ± 2%, and systemic vascular resistanceincreased 10 ± 3% (both P < 0.05). When hyperthermia wasprevented, all of the decline in SV with dehydration was due to reducedblood volume (~200 ml). These results demonstrate that thesuperimposition of dehydration on hyperthermia during exercise in theheat causes an inability to maintain cardiac output and blood pressurethat makes the dehydrated athlete less able to cope with hyperthermia.

     

Reproductive function in male endurance athletes: sperm analysis and hormonal profile

Lucía, Alejandro, José L. Chicharro, MargaritaPérez, Luis Serratosa, Fernando Bandrés, and Julio C. Legido. Reproductive function in male endurance athletes: spermanalysis and hormonal profile. J. Appl.Physiol. 81(6): 2627-2636, 1996.The purpose ofthis investigation was to study the effects of endurance exercise onmale reproductive function (sex hormones and seminograms). Professionalcyclists [n = 12; mean age 24 ± 2 (SD) yr], elite triathletes(n = 9; 26 ± 3 yr),recreational marathon runners (n = 10;32 ± 6 yr), and sedentary subjects (control group;n = 9; 30 ± 4 yr) were selected assubjects. For each group, the following parameters were measured threetimes during the sports season (training period: winter; competitionperiod: spring; resting period: fall): percentage of body fat, hormonalprofile (resting levels of follicle-stimulating hormone, luteinizinghormone, total and free testosterone, and cortisol), and seminograms(quantitative parameters: sperm volume and sperm count; qualitativeparameters: sperm motility and morphology). The following comparisonswere made in the measured parameters:1) within groups (longitudinal design) and 2) between groups ineach of the three periods (cross-sectional design) and over time (mixeddesign). In addition, both the volume and the intensity of training ofeach subject during the season (except for the control group) werequantified. Despite significant differences in training characteristicsand in body fat percent, in general no significant differences(P > 0.05) were found in hormonalprofiles or in semen characteristics between or within groups. A lowersperm motility (46.2 ± 19.5%), however, was observed in thecyclists during the competition period when compared either with theother groups during this same period(P < 0.05) or with themselves duringthe other two periods of study (P < 0.01). In any case, the later phenomenon was attributed to physicalfactors associated with cycling, such as mechanical trauma to thetestis and/or increased gonadal temperature. In conclusion, ourfindings suggest that endurance exercise does not adversely affect the hypothalamic-pituitary-testis axis.

     

Skeletal muscle chemoreflex and pHi in exercise ventilatory control

Oelberg, David A., Allison B. Evans, Mirko I. Hrovat, PaulP. Pappagianopoulos, Samuel Patz, and David M. Systrom. Skeletal muscle chemoreflex and pH_i inexercise ventilatory control. J. Appl.Physiol. 84(2): 676-682, 1998.To determinewhether skeletal muscle hydrogen ion mediates ventilatory drive inhumans during exercise, 12 healthy subjects performed three bouts ofisotonic submaximal quadriceps exercise on each of 2 days in a 1.5-Tmagnet for ³¹P-magnetic resonancespectroscopy(³¹P-MRS). Bilaterallower extremity positive pressure cuffs were inflated to 45 Torr duringexercise (BLPP_ex) or recovery(BLPP_rec) in a randomized orderto accentuate a muscle chemoreflex. Simultaneous measurements were madeof breath-by-breath expired gases and minute ventilation, arterializedvenous blood, and by ³¹P-MRS ofthe vastus medialis, acquired from the average of 12 radio-frequencypulses at a repetition time of 2.5 s. WithBLPP_ex, end-exercise minuteventilation was higher (53.3 ± 3.8 vs. 37.3 ± 2.2 l/min;P < 0.0001), arterializedPCO₂ lower (33 ± 1 vs. 36 ± 1 Torr; P = 0.0009), and quadricepsintracellular pH (pH_i) more acid (6.44 ± 0.07 vs. 6.62 ± 0.07; P = 0.004), compared withBLPP_rec. Bloodlactate was modestly increased withBLPP_ex but without a change inarterialized pH. For each subject, pH_i was linearly relatedto minute ventilation during exercise but not to arterialized pH. Thesedata suggest that skeletal muscle hydrogen ion contributes to theexercise ventilatory response.

     

Supercritical fluid-aerosolized vitamin E pretreatment decreases leak in isolated oxidant-perfused rat lungs

Hybertson, Brooks M., Roger P. Kitlowski, Eric K. Jepson,and John E. Repine. Supercritical fluid-aerosolized vitamin Epretreatment decreases leak in isolated oxidant-perfused rat lungs.J. Appl. Physiol. 84(1): 263-268, 1998.We hypothesized that direct pulmonary administration ofsupercritical fluid-aerosolized (SFA) vitamin E would decrease acuteoxidative lung injury. We previously reported that rapid expansion ofsupercritical CO₂ formedrespirable particles of vitamin E and that administering SFA vitamin Eto rats increased lung vitamin E levels and decreased neutrophil-mediated lung leak. In the present investigation, we foundthat pretreatment with SFA vitamin E protected isolated rat lungsagainst the oxidant-induced lung leak caused by perfusion with xanthineoxidase (XO) and purine, an enzyme system that generates superoxideanion () and hydrogenperoxide. SFA vitamin E droplets were 0.7-3 µm in diameter, andinhalation of the airborne droplets for 30 min deposited ~55 µg ofvitamin E in rat lungs. Isolated rat lungs perfused with XO (0.02 U/ml) and purine (10 mM) gained more weight (1.75 ± 0.12 g,n = 8), retained more Ficoll(11.5 ± 1.2 mg/left lung,n = 7), and accumulated more Ficoll intheir lung lavages (700 ± 146 µg/ml,n = 8) than control lungs [0.25 ± 0.06 g (n = 10), 6.2 ± 1.2 mg/left lung (n = 9), and 141 ± 31 µg/ml (n = 8), respectively,P < 0.05]. In contrast,isolated lungs from rats that were pretreated with SFA vitamin E haddecreased (P < 0.05) weight gains(0.32 ± 0.06 g, n = 7), Ficollretentions (3.3 ± 1.1 mg/left lung,n = 7), and lung lavage Ficollconcentrations (91 ± 26 µg/ml,n = 6) after perfusion with XO andpurine compared with isolated lungs from control rats perfused with XOand purine. This protective effect was not observed in rat lungs givensham treatments (CO₂ alone orvitamin E acetate aerosolized with supercriticalCO₂). Our results suggest thatdirect pulmonary supplementation of vitamin E decreases susceptibilityto vascular leakage caused by XO-derived oxidants.

     

Fuel metabolism in men and women during and after long-duration exercise

This study aimed to determine gender-baseddifferences in fuel metabolism in response to long-duration exercise.Fuel oxidation and the metabolic response to exercise were compared inmen (n = 14) and women(n = 13) during 2 h (40% of maximalO₂ uptake) of cycling and 2 h ofpostexercise recovery. In addition, subjects completed a separatecontrol day on which no exercise was performed. Fuel oxidation wasmeasured using indirect calorimetry, and blood samples were drawn forthe determination of circulating substrate and hormone levels. Duringexercise, women derived proportionally more of the total energyexpended from fat oxidation (50.9 ± 1.8 and 43.7 ± 2.1% forwomen and men, respectively, P < 0.02), whereas men derived proportionally more energy from carbohydrateoxidation (53.1 ± 2.1 and 45.7 ± 1.8% for men and women,respectively, P < 0.01). Thesegender-based differences were not observed before exercise, afterexercise, or on the control day. Epinephrine(P < 0.007) and norepinephrine(P < 0.0009) levels weresignificantly greater during exercise in men than in women (peakepinephrine concentrations: 208 ± 36 and 121 ± 15 pg/ml in menand women, respectively; peak norepinephrine concentrations: 924 ± 125 and 659 ± 68 pg/ml in men and women, respectively). Ascirculating glycerol levels were not different between the two groups,this suggests that women may be more sensitive to the lipolytic action of the catecholamines. In conclusion, these data support the view thatdifferent priorities are placed on lipid and carbohydrate oxidationduring exercise in men and women and that these gender-based differences extend to the catecholamine response to exercise.

     

Reduced oxidation rates of ingested glucose during prolonged exercise with low endogenous CHO availability

Jeukendrup, Asker E., Lars B. Borghouts, Wim H. M. Saris,and Anton J. M. Wagenmakers. Reduced oxidation rates of ingested glucose during prolonged exercise with low endogenous CHO availability. J. Appl. Physiol. 81(5):1952-1957, 1996.This study investigated the effect of endogenouscarbohydrate (CHO) availability on oxidation rates of ingested glucoseduring moderate-intensity exercise. Seven well-trained cyclistsperformed two trials of 120 min of cycling exercise in random order at57% maximal O₂ consumption. Preexercise glycogen concentrations were manipulated byglycogen-lowering exercise in combination with CHO restriction[low-glycogen (LG) trial] or CHO loading[moderate-to-high-glycogen (HG) trial]. In the LG and HGtrials, subjects ingested 4 ml/kg body wt of an 8% corn-derivedglucose solution of high natural¹³C abundance at the start,followed by boluses of 2 ml/kg every 15 min. The third trial, in whichpotato-derived glucose was ingested, served as a control test forbackground correction. Exogenous glucose oxidation rates werecalculated from the ¹³C enrichmentof the ingested glucose and of the breathCO₂. Total CHO oxidation was lowerin the LG trial than in the HG trial during 60-120 min of exercise[84 ± 7 (SE) vs. 116 ± 8 g;P < 0.05]. Exogenous CHOoxidation in this period was 28% lower in the LG trial compared withthe HG trial. Maximal exogenous oxidation rates were also lower(P < 0.05) in the LG trial (0.64 ± 0.05 g/min) than in the HG trial (0.88 ± 0.04 g/min). Thisdecreased utilization of exogenous glucose was accompanied by increased plasma free fatty acid levels (2-3 times higher) and lower insulin concentrations. It is concluded that glycogen-lowering exercise, performed the evening before an exercise bout, in combination with CHOrestriction leads to a reduction of the oxidation rate of ingestedglucose during moderate-intensity exercise.

     

Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction

Charan, Nirmal B., and Paula Carvalho. Angiogenesis inbronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1):284-291, 1997.We studied the effects of left pulmonary artery(LPA) ligation on the bronchial circulatory system (BCS) by using asheep model. LPA was ligated in the newborn lambs soon after birth(n = 8), and when the sheep were ~3yr of age anatomic studies revealed marked angiogenesis in BCS.Bronchial blood flow and cardiac output were studied by placing flowprobes around the bronchial and pulmonary arteries in four adult sheep.After LPA ligation, bronchial blood flow increased from 35 ± 6 to134 ± 42 ml/min in ~3 wk (P < 0.05). We also studied gas-exchange functions of BCS ~3 yr after the ligation of LPA in newborn lambs (n = 4) and used a control group (n = 12)in which LPA was ligated acutely. In the left lung,O₂ uptake after acute ligation was16 ± 3 ml/min and was similar to the chronic model, whereasCO₂ output in the control group was 27 ± 3 ml/min compared with 79 ± 12 ml/min in the chronic preparation (P < 0.05).We conclude that LPA ligation causes marked angiogenesis in BCS that iscapable of performing some gas-exchange functions.

     

Role of inhibition of nitric oxide production in monocrotaline-induced pulmonary hypertension

Mathew, Rajamma, Elizabeth S. Gloster, T. Sundararajan, Carl I. Thompson, Guillermo A. Zeballos, andMichael H. Gewitz. Role of inhibition of nitric oxide productionin monocrotaline-induced pulmonary hypertension. J. Appl. Physiol. 82(5): 1493-1498, 1997.Monocrotaline (MCT)-induced pulmonary hypertension (PH) isassociated with impaired endothelium-dependent nitric oxide(NO)-mediated relaxation. To examine the role of NO in PH,Sprague-Dawley rats were given a single subcutaneous injection ofnormal saline [control (C)], 80 mg/kg MCT, or the same doseof MCT and a continuous subcutaneous infusion of 2 mg · kg¹ · day¹of molsidomine, a NO prodrug (MCT+MD). Two weeks later, plasma NO₃ levels, pulmonary arterialpressure (Ppa), ratio of right-to-left ventricular weights (RV/LV) toassess right ventricular hypertrophy, and pulmonary histology wereevaluated. The plasma NO₃ level inthe MCT group was reduced to 9.2 ± 1.5 µM(n = 12) vs. C level of 17.7 ± 1.8 µM (n = 8; P < 0.02). In the MCT+MD group,plasma NO₃ level was 12.3 ± 2.0 µM (n = 8). Ppa and RV/LV in theMCT group were increased compared with C [Ppa, 34 ± 3.4 mmHg(n = 6) vs. 19 ± 0.8 mmHg(n = 8) and 0.41 ± 0.01 (n = 9) vs. 0.25 ± 0.008 (n = 8), respectively;P < 0.001]. In the MCT+MDgroup, Ppa and RV/LV were not different when compared with C [19 ± 0.5 mmHg (n = 5) and 0.27 ± 0.01 (n = 9), respectively;P < 0.001 vs. MCT]. Medial wall thickness of lung vessels in the MCT group was increased comparedwith C [31 ± 1.5% (n = 9)vs. 13 ± 0.66% (n = 9);P < 0.001], and MDpartially prevented MCT-induced pulmonary vascular remodeling [22 ± 1.2% (n = 11);P < 0.001 vs. MCT and C].These results indicate that a defect in the availability of bioactive NO may play an important role in the pathogenesis of MCT-induced PH.

     

Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia

Albert, T. S. E., V. L. Tucker, and E. M. Renkin.Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia. J. Appl.Physiol. 82(1): 102-110, 1997.Arterial oxygentensions (Pa_O2), atrial natriureticpeptide (ANP) concentrations, and circulating plasma volumes (PV) weremeasured in anesthetized rats ventilated with room air or 15, 10, or8% O₂(n = 5-7). After 10 min ofventilation, Pa_O2 values were 80 ± 3, 46 ± 1, 32 ± 1, and 35 ± 1 Torrand plasma immunoreactive ANP (irANP) levels were 211 ± 29, 229 ± 28, 911 ± 205, and 4,374 ± 961 pg/ml, respectively. AtPa_O2 40 Torr, irANP responses weremore closely related to inspiredO₂(P = 0.014) than toPa_O2 (P = 0.168). PV was 36.3 ± 0.5 µl/g in controls but 8.5 and9.9% lower (P  0.05) for10 and 8% O₂, respectively.Proportional increases in hematocrit were observed in animals withreduced PV; however, plasma protein concentrations were not differentfrom control. Between 10 and 50 min of hypoxia, small increases (+40%)in irANP occurred in 15% O₂;however, there was no further change in PV, hematocrit, plasma protein,or irANP levels in the lower O₂groups. Urine output tended to fall during hypoxia but was notsignificantly different among groups. These findings are compatiblewith a role for ANP in mediating PV contraction during acute alveolarhypoxia.

     

Ventilatory response to exercise in subjects breathing CO2 or HeO2

Babb, T. G. Ventilatory response to exercise insubjects breathing CO₂ orHeO₂.J. Appl. Physiol. 82(3): 746-754, 1997.To investigate the effects of mechanical ventilatory limitationon the ventilatory response to exercise, eight older subjects with normal lung function were studied. Each subject performed graded cycleergometry to exhaustion once while breathing room air; once whilebreathing 3% CO₂-21%O₂-balanceN₂; and once while breathing HeO₂ (79% He and 21%O₂). Minute ventilation(E) and respiratory mechanics weremeasured continuously during each 1-min increment in work rate (10 or20 W). Data were analyzed at rest, at ventilatory threshold (VTh),and at maximal exercise. When the subjects were breathing 3%CO₂, there was an increase(P < 0.001) inE at rest and at VTh but not duringmaximal exercise. When the subjects were breathingHeO₂,E was increased(P < 0.05) only during maximalexercise (24 ± 11%). The ventilatory response to exercise belowVTh was greater only when the subjects were breathing 3% CO₂(P < 0.05). Above VTh, theventilatory response when the subjects were breathingHeO₂ was greater than whenbreathing 3% CO₂(P < 0.01). Flow limitation, aspercent of tidal volume, during maximal exercise was greater(P < 0.01) when the subjects werebreathing CO₂ (22 ± 12%) thanwhen breathing room air (12 ± 9%) or when breathingHeO₂ (10 ± 7%)(n = 7). End-expiratory lung volumeduring maximal exercise was lower when the subjects were breathingHeO₂ than when breathing room airor when breathing CO₂(P < 0.01). These data indicate thatolder subjects have little reserve for accommodating an increase inventilatory demand and suggest that mechanical ventilatory constraintsinfluence both the magnitude of Eduring maximal exercise and the regulation ofE and respiratory mechanics duringheavy-to-maximal exercise.

     

Effect of an 18-wk weight-training program on energy expenditure and physical activity

Van Etten, Ludo M. L. A., Klaas R. Westerterp, Frans T. J. Verstappen, Bart J. B. Boon, and Wim H. M. Saris. Effect of an18-wk weight-training program on energy expenditure and physicalactivity. J. Appl. Physiol. 82(1):298-304, 1997.The purpose of this study was to examine theeffect of an 18-wk weight-training program on average daily metabolicrate (ADMR). Before the intervention and in weeks8 and 18 (T₀,T₈, andT₁₈, respectively) data on bodycomposition, sleeping metabolic rate (SMR), food intake, energy cost ofthe weight-training program(EE_ex), and nontraining physicalactivity (accelerometer) were collected in the exercise group (EXER,n = 18 males). ADMR was determined ina subgroup (EX12, n = 12) by usingdoubly labeled water. At T₀ andT₁₈, data (except ADMR) were alsocollected in a control group (Con, n = 8). Body mass did not change in EXER or Con. Fat-free mass increased only in EXER with 2.1 ± 1.2 kg, whereas fat mass decreased in EXERas well as Con (2.0 ± 1.8 and 1.4 ± 1.0 kg, respectively). Initial ADMR (12.4 ± 1.2 MJ/day) increased atT₈ (13.5 ± 1.3 MJ/day, P < 0.001) with no further increaseat T₁₈ (13.5 ± 1.9 MJ/day). SMR did not change in EXER (4.8 ± 0.5, 4.9 ± 0.5, 4.8 ± 0.5 kJ/min) or Con (4.7 ± 0.4, 4.8 ± 0.4 kJ/min). Energy intake didnot change in EXER (10.1 ± 1.8, 9.7 ± 1.8, 9.2 ± 1.9 MJ/day) or Con (10.2 ± 2.6, 9.4 ± 1.8, 10.1 ± 1.5 MJ/day)and was systematically underreported in EX12 (21 ± 14, 28 ± 18, 34 ± 14%,P < 0.001).EE_ex (0.47 ± 0.20, 0.50 ± 0.18 MJ/day) could only explain 40% of the increase in ADMR.Nontraining physical activity did not change in both groups. Inconclusion, although of modest energy cost, weight-training induces asignificant increase in ADMR.

     

Effect of supplemental oxygen on supramaximal exercise performance and recovery in cystic fibrosis

Shah, Ashish R., Thomas G. Keens, and David Gozal.Effect of supplemental oxygen on supramaximal exercise performance and recovery in cystic fibrosis. J. Appl.Physiol. 83(5): 1641-1647, 1997.The effects ofsupplemental O₂ on recovery fromsupramaximal exercise and subsequent performance remain unknown. Ifrecovery from exercise could be enhanced in individuals with chroniclung disease, subsequent supramaximal exercise performance could also be improved. Recovery from supramaximal exercise and subsequent supramaximal exercise performance were assessed after 10 min of breathing 100% O₂ or room air(RA) in 17 cystic fibrosis (CF) patients [25 ± 10 (SD) yrold, 53% men, forced expired volume in 1 s = 62 ± 21%predicted] and 17 normal subjects (25 ± 8 yr old, 59% men,forced expired volume in 1 s = 112 ± 15% predicted). Supramaximalperformance was assessed as the work of sustained bicycling at a loadof 130% of the maximum load achieved during a graded maximal exercise.Peak minute ventilation(E) andheart rate (HR) were lower in CF patients at the end of eachsupramaximal bout than in controls. In CF patients, single-exponentialtime decay constants indicated faster recovery of HR(_HR = 86 ± 8 and 73 ± 6 s in RA and O₂,respectively, P < 0.01). Similarly, fast and slow time constants of two-exponential equations providing thebest fit for ventilatory recovery were improved in CF patients duringO₂ breathing ( = 132.1 ± 10.5 vs. 82.5 ± 10.4 s; = 880.3 ± 300.1 vs. 368.6 ± 107.1 s,P < 0.01). However, no such improvements occurred in controls. Supramaximal performance after O₂ improved in CF patients (109 ± 6% of the 1st bout after O₂ vs. 94 ± 6% in RA, P < 0.01).O₂ supplementation had no effect on subsequent performance in controls (97 ± 3% inO₂ vs. 93 ± 3% in RA). Weconclude that supplemental O₂after a short bout of supramaximal exercise accelerates recovery andpreserves subsequent supramaximal performance in patients with CF.

     

Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia

Haskell, Andrew, Ethan R. Nadel, Nina S. Stachenfeld, KeiNagashima, and Gary W. Mack. Transcapillary escape rate of albuminin humans during exercise-induced hypervolemia. J. Appl. Physiol. 83(2): 407-413, 1997.To test thehypotheses that plasma volume (PV) expansion 24 h after intenseexercise is associated with reduced transcapillary escape rate ofalbumin (TER_alb) and that localchanges in transcapillary forces in the previously active tissues favorretention of protein in the vascular space, we measured PV,TER_alb, plasma colloid osmoticpressure (COP_p), interstitialfluid hydrostatic pressure (Pi), and colloid osmotic pressure in legmuscle and skin and capillary filtration coefficient (CFC) in the armand leg in seven men and women before and 24 h after intense uprightcycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 ± 0.8 to 46.8 ± 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 ± 0.1 to6.3 ± 0.1 g/dl, P < 0.05) andCOP_p (26.1 ± 0.8 to 24.3 ± 0.9 mmHg, P < 0.05), although plasmaalbumin concentration was unchanged. TER_alb tended to decline (8.4 ± 0.5 to 6.5 ± 0.7%/h, P = 0.11) and was correlated with the increase in PV(r = 0.69,P < 0.05). CFC increased in the leg(3.2 ± 0.2 to 4.3 ± 0.5 µl · 100 g¹ · min¹ · mmHg¹,P < 0.05), and Pi showed a trend toincrease in the leg muscle (2.8 ± 0.7 to 3.8 ± 0.3 mmHg, P = 0.08). These datademonstrate that TER_alb isassociated with PV regulation and that local transcapillary forcesin the leg muscle may favor retention of albumin in the vascular spaceafter exercise.

     

Effects of the ovarian cycle on sympathetic neural outflow during static exercise

We comparedreflex responses to static handgrip at 30% maximal voluntarycontraction (MVC) in 10 women (mean age 24.1 ± 1.7 yr) during twophases of their ovarian cycle: the menstrual phase (days 1-4) and the follicularphase (days10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response tostatic exercise were greater during the menstrual compared withfollicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase(75 ± 5.5 vs. 116 ± 9.6 pg/ml, days 1-4 vs.days 10-12;P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 ± 1.3 vs. 28.2 ± 1.5 kg, days 1-4 vs.days 10-12;P = 0.13). In a group of experiments with the use of ³¹P-NMRspectroscopy, no phase effect was observed forH⁺ andH₂PO₄ concentrations(n = 5). During an ischemicrhythmic handgrip paradigm (20% MVC), a phase effect was notobserved for MSNA or H⁺ orH₂PO₄ concentrations,suggesting that blood flow was necessary for the expression of thecycle-related effect. The present studies suggest that, during statichandgrip exercise, MSNA is increased during the menstrual compared withthe follicular phase of the ovarian cycle.

     

Cardiorespiratory responses to systemic administration of a protein kinase C inhibitor in conscious rats

Gozal, David, Gavin R. Graff, José E. Torres, SanjayG. Khicha, Gautam S. Nayak, Narong Simakajornboon, and Evelyne Gozal. Cardiorespiratory responses to systemic administration of aprotein kinase C inhibitor in conscious rats. J. Appl.Physiol. 84(2): 641-648, 1998.Although proteinkinase C (PKC) is an essential component of multiple neurally mediatedevents, its role in respiratory control remains undefined. Theventilatory effects of a systemically active PKC inhibitor (Ro-32-0432;100 mg/kg ip) were assessed by whole body plethysmography duringnormoxia, hypoxia (10% O₂), andhyperoxia (100% O₂) inunrestrained Sprague-Dawley rats. A sustained expiratory time increaseoccurred within 8-10 min of injection in room air[mean 44.8 ± 5.2 (SE) % ], was similarto expiratory time prolongations after Ro-32-0432 administration during100% O₂ (45.5 ± 8.1%; not significant), and was associated with mildminute ventilation (E) decreases.Hypercapnic ventilatory responses (5%CO₂) remained unchanged afterRo-32-0432. During 10% O₂,E increased from 122.6 ± 15.6 to 195.7 ± 10.1 ml/min in vehicle-treated rats(P < 0.001). In contrast, markedattenuation of E hypoxic responsesoccurred after Ro-32-0432 [86.2 ± 6.2 ml/min inroom air to 104.1 ± 7.1 ml/min in 10%O₂; pre- vs. post-Ro32-0432, P < 0.001 (analysis ofvariance)]. Overall, PKC activity was reduced and increases withhypoxia were abolished in the particulate subcellular fraction of brain tissue after Ro-32-0432 treatment, indicating thatthis compound readily crosses the blood-brain barrier. We conclude thatsystemic PKC inhibition elicits significant centrally mediatedexpiratory prolongations and ventilatory reductions as well as bluntedventilatory responses to hypoxia but not to hypercapnia. Wepostulate that PKC plays an important role in signal transduction pathways within brain regions underlying respiratory control.

     

Endothelial cell dilatory pathways link flow and wall shear stress in an intact arteriolar network

Frame, Mary D. S., and Ingrid H. Sarelius. Endothelialcell dilatory pathways link flow and wall shear stress in an intactarteriolar network. J. Appl. Physiol.81(5): 2105-2114, 1996.Our purpose was to determine whether theendothelial cell-dependent dilatory pathways contribute to theregulation of flow distribution in an intact arteriolar network. Cellflow, wall shear stress (T),diameter, and bifurcation angle were determined for four sequentialbranches of a transverse arteriole in the superfused cremaster muscleof pentobaribtal sodium (Nembutal, 70 mg/kg)-anesthetized hamsters(n = 51). Control cell flow wassignificantly greater into upstream than into downstream branches[1,561 ± 315 vs. 971 ± 200 (SE) cells/s,n = 12]. Tissue exposure to 50 µMN-nitro-L-arginine + 50 µM indomethacin (L-NNA + Indo) produced arteriolar constriction of 14 ± 4% and decreasedflow into the transverse arteriole. More of the available cell flow wasdiverted to downstream branches, yet flow distribution remainedunequal. Control T was higherupstream than downstream (31.3 ± 6.8 vs. 9.8 ± 1.5 dyn/cm²).L-NNA + Indo decreasedT upstream and increasedT downstream to become equal inall branches, in contrast to flow. To determine whether constriction ingeneral induced the same changes, 5%O₂ (8 ± 4% constriction) or10⁹ M norepinephrine (NE;4 ± 3% constriction) was added to the tissue (n = 7). WithO₂, flow was redistributed tobecome equal into each branch. With NE, flow decreased progressivelymore into the first three branches. The changes in flow distributionwere thus predictable and dependent on the agonist. WithO₂ or NE, the spatial changes inflow were mirrored by spatial changes inT. Changes in diameter and incell flux were not related forL-NNA + Indo (r = 0.45),O₂(r = 0.07), or NE(r = 0.36). For all agonists, when thebifurcation angle increased, cell flow to the branch decreasedsignificantly, whereas if the angle decreased, flow was relativelypreserved; thus active changes in bifurcation angle may influence redcell distribution at arteriolar bifurcations. Thus, when theendothelial cell dilatory pathways were blocked, the changes in flowand in T were uncoupled; yet when they were intact, flowand T changed together.

     

Prostaglandin production contributes to exercise-induced vasodilation in heart failure

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor,and John R. Wilson. Prostaglandin production contributes toexercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933-1940, 1997.Endothelial release of prostaglandins may contribute toexercise-induced skeletal muscle arteriolar vasodilation in patientswith heart failure. To test this hypothesis, we examined the effect ofindomethacin on leg circulation and metabolism in eight chronic heartfailure patients, aged 55 ± 4 yr. Central hemodynamics and legblood flow, determined by thermodilution, and leg metabolic parameterswere measured during maximum treadmill exercise before and 2 h afteroral administration of indomethacin (75 mg). Leg release of6-ketoprostaglandin F₁ was alsomeasured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min(P < 0.001), legO₂ consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to267.4 ± 35.8 pg/min (P < 0.001).Indomethacin suppressed release of prostaglandinF₁(P < 0.001) throughout exercise anddecreased leg blood flow during exercise(P < 0.05). This was associated witha corresponding decrease in leg O₂ consumption (P < 0.05) and a higher level offemoral venous lactate at peak exercise(P < 0.01). These data suggest thatrelease of vasodilatory prostaglandins contributes to skeletal musclearteriolar vasodilation in patients with heart failure.

     

Enhanced ventilatory and exercise performance in athletes with slight expiratory resistive loading

Fee, Lawrence L., Richard M. Smith, and Michael B. English.Enhanced ventilatory and exercise performance in athletes withslight expiratory resistive loading. J. Appl.Physiol. 83(2): 503-510, 1997.We determined thecardiorespiratory and performance effects of slight (1.5-3.0cmH₂O) expiratory resistiveloading (ERL). Twenty-eight highly fit [peakO₂ uptake(O_{2 peak}) = 63.6 ± 1.3 ml · kg¹ · min¹]athletes (age = 33.5 ± 1.3 yr) performed pairedO_{2 peak} cycle ergometer tests (control vs. ERL). End-expiratory lung volume wasseparately determined in a subset of subjects(n = 12) at steady-state 75% maximumpower output (PO_max) and wasfound to increase (0.67 ± 0.29 liter) with ERL. In theO_{2 peak}tests, peak expiratory pressure at the mouth, mean inspiratory flow, minute ventilation, and O₂ pulsewere greater with ERL at every intensity level (i.e., 75, 80, 85, and90% PO_max). Increased minute ventilation was largely due to a trend toward increased tidal volume(P < 0.05 at 80%PO_max).O₂ uptake was greater at 90%PO_max with ERL. IncreasedO₂ pulse with ERL at comparativeworkloads suggests that stroke volume was augmented with ERL. Also,with ERL, athletes attained higherO_{2 peak} (63.0 ± 1.4 vs. 60.1 ± 1.3 ml · kg¹ · min¹)and greater PO_max (352.0 ± 9.9 vs. 345.7 ± 9.5 W). We conclude that elevated end-expiratory lungvolume in response to slight ERL during strenuous exercise served toattenuate both airflow and blood flow limitations, which enhancedexercise capacity.

     

H2O2 increases sheep tracheal blood flow, permeability, and vascular response to luminal capsaicin

Wells, U. M., S. Duneclift, and J. G. Widdicombe.H₂O₂increases sheep tracheal blood flow, permeability, and vascular response to luminal capsaicin. J. Appl.Physiol. 82(2): 621-631, 1997.Exogenous hydrogenperoxide(H₂O₂)causes airway epithelial damage in vitro. We have studied the effectsof luminalH₂O₂in the sheep trachea in vivo on tracheal permeability tolow-molecular-weight hydrophilic (technetium-99m-labeleddiethylenetriamine pentaacetic acid;^99mTc-DTPA) and lipophilic([¹⁴C]antipyrine;[¹⁴C]AP) tracers andon the tracheal vascular response to luminal capsaicin, whichstimulates afferent nerve endings. A tracheal artery was perfused, andtracheal venous blood was collected. H₂O₂exposure (10 mM) reduced tracheal potential difference(42.0 ± 6.4 mV) to zero. It increased arterial andvenous flows (56.7 ± 6.1 and 57.3 ± 10.0%,respectively; n = 5, P < 0.01, paired t-test) but not tracheal lymph flow(unstimulated flow 5.0 ± 1.2 µl ^· min^{1 ·} cm¹,n = 4). DuringH₂O₂exposure, permeability to ^99mTc-DTPA increased from2.6 to 89.7 × 10⁷ cm/s(n = 5, P < 0.05), whereas permeability to[¹⁴C]AP (3,312.6 × 10⁷ cm/s,n = 4) was not altered significantly(2,565 × 10⁷cm/s). Luminal capsaicin (10 µM) increased tracheal blood flow (10.1 ± 4.1%, n = 5)and decreased venous ^99mTc-DTPAconcentration (19.7 ± 4.0, P < 0.01), and these effects weresignificantly greater after epithelial damage (28.1 ± 6.0 and45.7 ± 4.3%, respectively,P < 0.05, unpairedt-test). Thus H₂O₂increases the penetration of a hydrophilic tracer into tracheal bloodand lymph but has less effect on a lipophilic tracer. It also enhancesthe effects of luminal capsaicin on blood flow and tracer uptake.

     

Pharmacological modulation of ion transport across wild-type and DeltaF508 CFTR-expressing human bronchial epithelia

Forskolin,UTP, 1-ethyl-2-benzimidazolinone (1-EBIO), NS004, 8-methoxypsoralen(Methoxsalen; 8-MOP), and genistein were evaluated for theireffects on ion transport across primary cultures of human bronchialepithelium (HBE) expressing wild-type (wt HBE) and F508(F-HBE) cystic fibrosis transmembrane conductance regulator. In wtHBE, the baseline short-circuit current (I_sc)averaged 27.0 ± 0.6 µA/cm² (n = 350). Amiloride reduced this I_sc by 13.5 ± 0.5 µA/cm² (n = 317). In F-HBE,baseline I_sc was 33.8 ± 1.2 µA/cm² (n = 200), and amiloride reducedthis by 29.6 ± 1.5 µA/cm² (n = 116), demonstrating the characteristic hyperabsorption of Na⁺ associated with cystic fibrosis (CF). In wt HBE,subsequent to amiloride, forskolin induced a sustained,bumetanide-sensitive I_sc(I_sc = 8.4 ± 0.8 µA/cm²; n = 119). Addition ofacetazolamide, 5-(N-ethyl-N-isopropyl)-amiloride, and serosal 4,4'-dinitrostilben-2,2'-disulfonic acid further reduced I_sc, suggesting forskolin also stimulatesHCO₃ secretion. This was confirmed by ionsubstitution studies. The forskolin-induced I_scwas inhibited by 293B, Ba²⁺, clofilium, and quinine,whereas charybdotoxin was without effect. In F-HBE the forskolinI_sc response was reduced to 1.2 ± 0.3 µA/cm² (n = 30). In wt HBE, mucosal UTPinduced a transient increase in I_sc ( I_sc = 15.5 ± 1.1 µA/cm²;n = 44) followed by a sustained plateau, whereas inF-HBE the increase in I_sc was reduced to5.8 ± 0.7 µA/cm² (n = 13). In wtHBE, 1-EBIO, NS004, 8-MOP, and genistein increased I_sc by 11.6 ± 0.9 (n = 20), 10.8 ± 1.7 (n = 18), 10.0 ± 1.6 (n = 5), and 7.9 ± 0.8 µA/cm²(n = 17), respectively. In F-HBE, 1-EBIO, NS004, and8-MOP failed to stimulate Cl secretion. However, additionof NS004 subsequent to forskolin induced a sustained Clsecretory response (2.1 ± 0.3 µA/cm²,n = 21). In F-HBE, genistein alone stimulatedCl secretion (2.5 ± 0.5 µA/cm²,n = 11). After incubation of F-HBE at 26°C for24 h, the responses to 1-EBIO, NS004, and genistein were allpotentiated. 1-EBIO and genistein increased Na⁺ absorptionacross F-HBE, whereas NS004 and 8-MOP had no effect. Finally,Ca²⁺-, but not cAMP-mediated agonists, stimulatedK⁺ secretion across both wt HBE and F-HBE in aglibenclamide-dependent fashion. Our results demonstrate thatpharmacological agents directed at both basolateral K⁺ andapical Cl conductances directly modulate Clsecretion across HBE, indicating they may be useful in ameliorating theion transport defect associated with CF.