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.

     

Bronchial vasodilatory response to ionic and nonionic contrast media

Baile, Elisabeth M., Lu Wang, Lorraine Verburgt, and PeterD. Paré. Bronchial vasodilatory response to ionic andnonionic contrast media. J. Appl.Physiol. 82(3): 841-845, 1997.It has recentlybeen shown that bronchial arterial injection of conventional contrastmedium causes a significant increase in bronchial blood flow(br) and that this response is partially attenuatedafter infusion ofN-nitro-L-arginine(L-NNA). However, the precisemechanism for this increase in br is unknown. Inthis study we examined the effect of bronchial arterial injection ofconventional ionic as well as nonionic contrast media. We measuredbr in nine anesthetized, ventilated, open-chestsheep. br was recorded before (baseline) and at thepeak response to injection of 0.5 ml of either 0.9% saline (control;isosmolar with plasma), Omnipaque 300 (iohexol; nonionic), Conray 66 (sodium iothalamate; ionic), or 50% dextrose (viscouscontrol).

     

Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ

Repetitiveisometric tetanic contractions (1/s) of the caninegastrocnemius-plantaris muscle were studied either at optimal length(L_o) or shortlength (L_s;~0.9 · L_o),to determine the effects of initial length on mechanical and metabolicperformance in situ. Respective averages of mechanical and metabolicvariables were(L_o vs.L_s, allP < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension(P_o) = 544 vs. 174 (0.38 · P_o)g/g, maximal blood flow () = 2.0 vs. 1.4 ml · min¹ · g¹,and maximal oxygen uptake(O₂) = 12 vs. 9 µmol · min¹ · g¹.Tension at L_odecreased to0.64 · P_o over20 min of repetitive contractions, demonstrating fatigue; there were nosignificant changes in tension atL_s. In separatemuscles contracting atL_o, was set to that measured atL_s (1.1 ml · min¹ · g¹),resulting in decreased O₂(7 µmol · min¹ · g¹),and rapid fatigue, to0.44 · P_o. Thesedata demonstrate that 1)muscles at L_ohave higher andO₂ values than those at L_s;2) fatigue occurs atL_o with highO₂, adjusting metabolic demand (tension output) to match supply; and3) the lack of fatigue atL_s with lowertension, , andO₂ suggestsadequate matching of metabolic demand, set low by shortmuscle length, with supply optimized by low preload. Thesedifferences in tension andO₂ betweenL_o andL_s groupsindicate that muscles contracting isometrically at initial lengthsshorter than L_oare working under submaximal conditions.

     

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta -agonists

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response toinhaled -agonists. J. Appl.Physiol. 84(1): 215-221, 1998.We studied thedose-dependent effects of inhaled isoetharine HCl, a -adrenergicbronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow(br) in anesthetized sheep. Isoetharine resulted ina dose-dependent increase in br. With atotal dose of 17.5 mg, br increased from baselinevalues of 22 ± 3.4 (SE) to 60 ± 16 ml/min(P < 0.001), an effect independentof changes in cardiac output and systemic arterial pressure. To furtherstudy whether synthesis of endogenous nitric oxide (NO) affects-agonist-induced increases in br, weadministered isoetharine (20 mg) by inhalation before and after theNO-synthase inhibitorN-nitro-L-argininemethyl ester (L-NAME).Intravenous L-NAME (30 mg/kg) rapidly decreased br by ~80% of baseline,whereas L-NAME via inhalation(10 mg/kg) resulted in a delayed and smaller (~22%) decrease.Pretreatment with L-NAME viaboth routes of administration attenuated bronchial arterialvasodilation after subsequent challenge with isoetharine. We concludethat isoetharine via inhalation increases br in adose-dependent manner and that -agonist-induced relaxation ofvascular smooth muscle in the bronchial vasculature is partiallymediated via synthesis of NO.

     

Nitric oxide and beta -adrenergic agonist-induced bronchial arterial vasodilation

Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan,William H. Thompson, and Paula Carvalho. Nitric oxide and-adrenergic agonist-induced bronchial arterial vasodilation.J. Appl. Physiol. 82(2): 686-692, 1997.In anesthetized sheep, we measured bronchial blood flow(br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) givenfor 5 min and 5 ml of aerosolized isoetharine (1.49 × 10² M concentration).NO and isoetharine increased br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min,respectively (n = 5).Administration of NO immediately after isoetharine further increasedbr to 57.3 ± 15.1 ml/min. NO synthase inhibitorN-nitro-L-arginine methyl esterhydrochloride (L-NAME; 30 mg/kg, in 20 ml salinegiven iv) decreased br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiatevasodilator effects of each other. In three other sheep, afterL-NAME, three sequential doses of isoetharine increased br from 10.2 ± 3.4 to11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min,respectively, indicating that effects of isoetharine are predominantlymediated through synthesis of NO. When this was followed by threesequential administrations of NO, br increased by146, 172, and 185%, respectively. Thus in the bronchial circulationthere seems to be a close interaction between adenosine3,5-cyclic monophosphate- and guanosine3,5-cyclic monophosphate-mediated vasodilatation.

     

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.

     

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.

     

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.

     

Training-induced alterations of carbohydrate metabolism in women: women respond differently from men

We examined the hypothesis that glucose flux wasdirectly related to relative exercise intensity both beforeand after a 12-wk cycle ergometer training program [5days/wk, 1-h duration, 75% peakO₂ consumption(O_{2 peak})] inhealthy female subjects (n = 17; age23.8 ± 2.0 yr). Two pretraining trials (45 and 65% of O_{2 peak})and two posttraining trials [same absolute workload (65% of oldO_{2 peak})and same relative workload (65% of new O_{2 peak})] wereperformed on nine subjects by using a primed-continuous infusion of[1-¹³C]- and[6,6-²H]glucose.Eight additional subjects were studied by using[6,6-²H]glucose.Subjects were studied postabsorption for 90 min of rest and 1 h ofcycling exercise. After training, subjects increased O_{2 peak} by 25.2 ± 2.4%. Pretraining, the intensity effect on glucose kinetics wasevident between 45 and 65% ofO_{2 peak} with rates ofappearance (R_a: 4.52 ± 0.25 vs. 5.53 ± 0.33 mg · kg¹ · min¹),disappearance (R_d: 4.46 ± 0.25 vs. 5.54 ± 0.33 mg · kg¹ · min¹),and oxidation (R_ox: 2.45 ± 0.16 vs. 4.35 ± 0.26 mg · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% thanin the 45% trial. Training reducedR_a (4.7 ± 0.30 mg · kg¹ · min¹),R_d (4.69 ± 0.20 mg · kg¹ · min¹),and R_ox (3.54 ± 0.50 mg · kg¹ · min¹)at the same absolute workload (P  0.05). When subjects were tested at the same relative workload,R_a,R_d, andR_ox were not significantlydifferent after training. However, at both workloads after training,there was a significant decrease in total carbohydrate oxidation asdetermined by the respiratory exchange ratio. These results show thefollowing in young women: 1)glucose use is directly related to exercise intensity;2) training decreasesglucose flux for a given power output;3) when expressed asrelative exercise intensity, training does not affect the magnitude ofblood glucose flux during exercise; but4) training does reduce totalcarbohydrate oxidation.

     

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.

     

Contractile responsiveness of coronary arteries from exercise-trained rats

Parker, Janet L., Mildred L. Mattox, and M. Harold Laughlin.Contractile responsiveness of coronary arteries from exercise trained rats. J. Appl. Physiol. 83(2):434-443, 1997.The purpose of this study was to determine whetherexercise training alters vasomotor reactivity of rat coronary arteries.In vitro isometric microvessel techniques were used to evaluatevasomotor properties of proximal left anterior artery rings (1 ring peranimal) from exercise-trained rats (ET;n = 10) subjected to a 12-wk treadmill training protocol (32 m/min, 15% incline, 1 h/day, 5 days/wk) andcontrol rats (C; n = 6) restricted tocage activity. No differences in passive length-tension characteristicsor internal diameter (158 ± 9 and 166 ± 9 µm) were observedbetween vessesls of C and ET rats. Concentration-response curves toK⁺ (5-100 mM), prostaglandinF₂(10⁸-10⁴M), and norepinephrine(10⁸-10⁴)were unaltered (P > 0.05) incoronary rings from ET rats compared with C rats; however, lower valuesof the concentration producing 50% of the maximal contractile responsein rings from ET rats (P = 0.05)suggest that contractile sensitivity to norepinephrine wasenhanced. Vasorelaxation responses to sodium nitroprusside (10⁹-10⁴M) and adenosine(10⁹-10⁴M) were not different (P > 0.05)between vessels of C and ET rats. However, relaxation responses to theendothelium-dependent vasodilator acetylcholine (ACh;10¹⁰-10⁴M) were significantly blunted (P < 0.001) in coronary rings from ET animals; maximal ACh relaxationaveraged 90 ± 5 and 46 ± 12%, respectively, in vessels of Cand ET groups. In additional experiments, two coronary rings (proximaland distal) were isolated from each C(n = 7) and ET(n = 7) animal. Proximal coronaryartery rings from ET animals demonstrated decreased relaxationresponses to ACh; however, ACh-mediated relaxation of distal coronaryrings was not different between C and ET groups.N^G-monomethyl-L-arginine(inhibitor of nitric oxide synthase) blocked ACh relaxation of allrings. L-Arginine (substrate fornitric oxide synthase) did not improve the blunted ACh relaxation in proximal coronary artery rings from ET rats. These studies suggest thatexercise-training selectively decreases endothelium-dependent (ACh) butnot endothelium-independent (sodium nitroprusside) relaxation responsesof rat proximal coronary arteries; endothelium-dependent relaxation ofdistal coronary arteries is unaltered by training.

     

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.

     

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.

     

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

Endogenous nitric oxide (NO) influences acetylcholine-inducedbronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural responsein several species. This study was designed to determine the importanceof NO as a neurally derived modulator of ovine airway and bronchialvascular smooth muscle. We measured the response of pulmonaryresistance (RL) and bronchialblood flow (br) to vagal stimulationin 14 anesthetized, ventilated, open-chest sheep duringthe following conditions: 1)control; 2) infusion of the -agonist phenylephrine to reduce baseline br bythe same amount as would be produced by infusion ofN-nitro-L-arginine(L-NNA), a NO synthaseinhibitor; 3) infusion ofL-NNA(10² M); and4) after administration of atropine(1.5 mg/kg). The results showed that vagal stimulation produced anincrease in RL andbr in periods 1, 2, and 3 (P < 0.01) that was not affected byL-NNA. Afteratropine was administered, there was no increase inbr or RL. Invitro experiments on trachealis smooth muscle contracted with carbachol showed no effect ofL-NNA on neural relaxation butshowed a complete blockade with propranolol(P < 0.01). In conclusion, thevagally induced airway smooth muscle contraction and bronchial vasculardilation are not influenced by NO, and the sheep's trachealis muscle,unlike that in several other species, does not have inhibitorynonadrenergic, noncholinergic innervation.

     

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.

     

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.

     

Mitochondrial redox state as a potential detector of liver dysoxia in vivo

Dysoxia canbe defined as ATP flux decreasing in proportion toO₂ availability with preserved ATPdemand. Hepatic venous -hydroxybutyrate-to-acetoacetate ratio(-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detectthe onset of dysoxia. During partial dysoxia (as opposed to anoxia),however, flow may be adequate in some liver regions, diluting effluentfrom dysoxic regions, thereby rendering venous -OHB/AcAc unreliable.To address this concern, we estimated tissue ATP whilegradually reducing liver blood flow of swine to zero in a nuclearmagnetic resonance spectrometer. ATP flux decreasing withO₂ availability was taken asO₂ uptake(O₂) decreasing inproportion to O₂ delivery(O₂);and preserved ATP demand was taken as increasingP_i/ATP.O₂, tissueP_i/ATP, and venous -OHB/AcAcwere plotted againstO₂to identify critical inflection points. Tissue dysoxia required meanO₂for the group to be critical for bothO₂ and forP_i/ATP. CriticalO₂values for O₂ andP_i/ATP of 4.07 ± 1.07 and 2.39 ± 1.18 (SE) ml · 100 g¹ · min¹,respectively, were not statistically significantly different but notclearly the same, suggesting the possibility that dysoxia might havecommenced after O₂ begandecreasing, i.e., that there could have been"O₂ conformity." CriticalO₂for venous -OHB/AcAc was 2.44 ± 0.46 ml · 100 g¹ · min¹(P = NS), nearly the same as that forP_i/ATP, supporting venous -OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector ofdysoxia in liver.

     

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.

     

Training-induced alterations of glucose flux in men

Friedlander, Anne L., Gretchen A. Casazza, Michael A. Horning, Melvin J. Huie, and George A. Brooks. Training-induced alterations of glucose flux in men. J. Appl.Physiol. 82(4): 1360-1369, 1997.We examined thehypothesis that glucose flux was directly related to relative exerciseintensity both before and after a 10-wk cycle ergometer trainingprogram in 19 healthy male subjects. Two pretraining trials [45and 65% of peak O₂ consumption(O_{2 peak})] andtwo posttraining trials (same absolute and relative intensities as 65%pretraining) were performed for 90 min of rest and 1 h of cyclingexercise. After training, subjects increasedO_{2 peak} by9.4 ± 1.4%. Pretraining, the intensity effect on glucose kinetics was evident with rates of appearance(R_a; 5.84 ± 0.23 vs. 4.73 ± 0.19 mg · kg¹ · min¹),disappearance (R_d; 5.78 ± 0.19 vs. 4.73 ± 0.19 mg · kg¹ · min¹),oxidation (R_ox; 5.36 ± 0.15 vs. 3.41 ± 0.23 mg · kg¹ · min¹),and metabolic clearance (7.03 ± 0.56 vs. 5.20 ± 0.28 ml · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% than the 45%O_{2 peak} trial. WhenR_d was expressed as a percentage of total energy expended per minute(R_{d E}), there was nodifference between the 45 and 65% intensities. Training did reduceR_a (4.63 ± 0.25),R_d (4.65 ± 0.24),R_ox (3.77 ± 0.43), andR_{d E} (15.30 ± 0.40 to12.85 ± 0.81) when subjects were tested at the same absolute workload (P  0.05). However, whenthey were tested at the same relative workload,R_a,R_d, andR_{d E} were not different,although R_ox was lowerposttraining (5.36 ± 0.15 vs. 4.41 ± 0.42, P  0.05). These results show1) glucose use is directly relatedto exercise intensity; 2) trainingdecreases glucose flux for a given power output;3) when expressed as relativeexercise intensity, training does not affect the magnitude of bloodglucose use during exercise; 4)training alters the pathways of glucose disposal.

     

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.