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.

     

Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes

Zhang, Xue-Qian, Yuk-Chow Ng, Timothy I. Musch, Russell L. Moore, R. Zelis, and Joseph Y. Cheung. Sprint training attenuates myocyte hypertrophy and improvesCa²⁺ homeostasis in postinfarctionmyocytes. J. Appl. Physiol. 84(2): 544-552, 1998.Myocytes isolated from rat hearts 3 wk aftermyocardial infarction (MI) had decreasedNa⁺/Ca²⁺exchange currents(I_Na/Ca; 3 Na⁺ out:1Ca²⁺ in) and sarcoplasmicreticulum (SR)-releasable Ca²⁺contents. These defects in Ca²⁺regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardialCa²⁺ regulation, thepresent study examined whether 6-8 wk ofhigh-intensity sprint training (HIST) would ameliorate some of thecellular maladaptations observed in post-MI rats with limited exerciseactivity (Sed). In MI rats, HIST did not affect citrate synthaseactivities of plantaris muscles but significantly increased thepercentage of cardiac -myosin heavy chain (MHC) isoforms (57.2 ± 1.9 vs. 49.3 ± 3.5 in MI-HIST vs. MI-Sed, respectively;P  0.05). At the single myocytelevel, HIST attenuated cellular hypertrophy observed post-MI, asevidenced by reductions in cell lengths (112 ± 4 vs. 130 ± 5 µm in MI-HIST vs. MI-Sed, respectively;P  0.005) and cell capacitances (212 ± 8 vs. 242 ± 9 pF in MI-HIST vs. MI-Sed, respectively; P  0.015). ReverseI_Na/Ca wassignificantly lower (P  0.0001) inmyocytes from MI-Sed rats compared with those from rats that were shamoperated and sedentary. HIST significantly increased reverseI_Na/Ca(P  0.05) without affecting theamount ofNa⁺/Ca²⁺exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca²⁺ content, as estimated byintegrating forwardI_Na/Ca duringcaffeine-induced SR Ca²⁺ release,was also significantly increased (P  0.02) by HIST in MI myocytes. We conclude that the enhanced cardiacoutput and stroke volume in post-MI rats subjected to HIST aremediated, at least in part, by reversal of cellular maladaptationspost-MI.

     

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.

     

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.

     

Contribution of nitric oxide and prostaglandins to reactive hyperemia in the human forearm

Engelke, Keith A., John R. Halliwill, David N. Proctor, NikiM. Dietz, and Michael J. Joyner. Contribution of nitric oxide andprostaglandins to reactive hyperemia in the human forearm. J. Appl. Physiol. 81(4):1807-1814, 1996.We investigated the separate and combinedcontributions of nitric oxide (NO) and vasodilating prostaglandins asmediators of reactive hyperemia in the human forearm. Forearm bloodflow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol (n = 12), measurements were made before and after intra-arterialadministration of the NO synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) to one forearm. In aseparate protocol (n = 7),measurements were made before and after systemic administration of thecyclooxygenase inhibitor ibuprofen and again afterL-NMMA.L-NMMA reduced baseline FBF atrest (2.7 ± 0.4 to 1.6 ± 0.2 ml ^· 100 ml^{1 ·} min¹;P < 0.05) and had a modesteffect on peak forearm vascular conductance and flow (forearm vascularconductance = 31.1 ± 3.1 vs. 25.7 ± 2.5 ml ^· min^{1 ·} 100 mlforearm^{1 ·} 100 mmHg of perfusionpressure^{1 ·} min¹,P < 0.05; FBF = 26.6 ± 2.9 vs.22.8 ± 2.6 ml ^· 100 ml^{1 ·} min¹,P = 0.055). Total excessflow above baseline during reactive hyperemia was unaffected byL-NMMA (14.3 ± 3.0 vs. 13.1 ± 2.3 ml/100 ml; P < 0.05).Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 ± 1.9 to 20.3 ± 2.7 ml ^· 100 ml^{1 ·} min¹(P < 0.05), but had no effect ontotal excess flow above baseline. Infusion ofL-NMMA after ibuprofen reducedFBF at rest by 40%, had no effect on peak flow, but reduced totalexcess flow above baseline from 12.0 ± 2.5 to 7.6 ± 1.3 ml/100ml (P < 0.05). These datademonstrate that NO synthase inhibition has a modest effect on peakvasodilation during reactive hyperemia but plays a minimal role later.Prostaglandins appear to be important determinants of peak flow. Theeffects of NO synthase inhibition during reactive hyperemia may also bepotentiated by concurrent cyclooxygenase inhibition.

     

Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans

To evaluatewhether interferon- (IFN-) is involved in the interaction betweenthe immune and endocrine systems in vivo, we studied six healthysubjects twice in a placebo-controlled trial: once after administrationof recombinant human IFN- and, on another occasion, afteradministration of saline. The rate of appearance of glucose wasdetermined by infusion of[6,6-²H₂]glucoseand resting energy expenditure by indirect calorimetry. Human leukocyteantigen-DR gene expression on monocytes and serum neopterin increased after administration of IFN-(P < 0.05 vs. control). IFN-increased serum interleukin-6 levels significantly. Levels of tumornecrosis factor- remained below detection limits. IFN- increasedplasma concentrations of ACTH and cortisol(P < 0.05 vs. control), IFN- didnot alter concentrations of growth hormone,(nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growthfactor I. IFN- did not alter plasma concentrations of glucose andfree fatty acids nor the rate of appearance of glucose. IFN-increased resting energy expenditure significantly. We conclude thatIFN- is a minor stimulator of the endocrine and metabolic pathways.Therefore, IFN- by itself is probably not a major mediator in theinteraction between the immune and the endocrine and metabolic systems.     

Low energy availability, not stress of exercise, alters LH pulsatility in exercising women

Loucks, A. B., M. Verdun, and E. M. Heath. Low energyavailability, not stress of exercise, alters LH pulsatility in exercising women. J. Appl. Physiol.84(1): 37-46, 1998.We tested two hypotheses about the disruptionof luteinizing hormone (LH) pulsatility in exercising women by assayingLH in blood samples drawn at 10-min intervals over 24 h from nineyoung, habitually sedentary, regularly menstruating women ondays 8,9, or10 of two menstrual cycles after 4 days of intense exercise [E = 30 kcal · kg leanbody mass(LBM)¹ · day¹at 70% of aerobic capacity]. To test the hypothesis that LHpulsatility is disrupted by low energy availability, we controlled thesubjects' dietary energy intakes (I) to set theirenergy availabilities (A = I  E) at 45 and 10 kcal · kgLBM¹ · day¹during the two trials. To test the hypothesis that LH pulsatility isdisrupted by the stress of exercise, we compared the resulting LHpulsatilities to those previously reported in women with similar controlled energy availability who had not exercised. In the exercising women, low energy availability reduced LH pulse frequency by 10% (P < 0.01) during thewaking hours and increased LH pulse amplitude by 36%(P = 0.05) during waking and sleepinghours, but this reduction in LH pulse frequency was blunted by 60%(P = 0.03) compared with that in thepreviously studied nonexercising women whose low energy availabilitywas caused by dietary restriction. The stress of exercise neitherreduced LH pulse frequency nor increased LH pulse amplitude (allP > 0.4). During exercise, theproportion of energy derived from carbohydrate oxidation was reducedfrom 73% while A = 45 kcal · kgLBM¹ · day¹to 49% while A = 10 kcal · kgLBM¹ ·day¹(P < 0.0001). These resultscontradict the hypothesis that LH pulsatility is disrupted by exercisestress and suggest that LH pulsatility in women depends on energyavailability.

     

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.

     

Tumor necrosis factor-alpha in ischemia and reperfusion injury in rat lungs

The effects ofboth recombinant rat tumor necrosis factor- (TNF-) and ananti-TNF- antibody were studied in isolated buffer-perfused ratlungs subjected to either 45 min of nonventilated[ischemia-reperfusion (I/R)] or air-ventilated(/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascularpermeability, as measured by the filtration coefficient(K_fc),increased three- and fivefold above baseline after 30 and 90 min ofreperfusion, respectively (P < 0.001). Over the same time intervals, theK_fc for the/R group increased five- and tenfold above baseline values, respectively (P < 0.001).TNF- measured in the perfusates of both ischemic modelssignificantly increased after 30 min of reperfusion. Recombinant ratTNF- (50,000 U), placed into perfusate after baseline measurements,produced no measurable change in microvascular permeability in controllungs perfused over the same time period (135 min), but I/R injury wassignificantly enhanced in the presence of TNF-. An anti-TNF-antibody (10 mg/rat) injected intraperitoneally into rats 2 h beforethe lung was isolated prevented the microvascular damage in lungsexposed to both I/R and /R (P < 0.001). These results indicatethat TNF- is an essential component at the cascade of events thatcause lung endothelial injury in short-term I/R and/R models of lung ischemia.

     

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.

     

Reductions in visceral fat during weight loss and walking are associated with improvements in {V}O2 max

The accumulation ofvisceral fat is independently associated with an increased risk forcardiovascular disease. The aim of this study was to determine whetherthe loss of visceral adipose tissue area (VAT; computed tomography) isrelated to improvements in maximal O₂ uptake(O_2 max) during a weight loss(250-350 kcal/day deficit) and walking (3 days/wk, 30-40 min)intervention. Forty obese [body fat 47 ± 1 (SE) %], sedentary(O_2 max 19 ± 1 ml · kg¹ · min¹)postmenopausal women (age 62 ± 1 yr) participated in the study. The intervention resulted in significant declines in body weight (8%), total fat mass (dual-energy X-ray absorptiometry; 17%), VAT(17%), and subcutaneous adipose tissue area (17%) with no changein lean body mass (all P < 0.001). Women with anaverage 10% increase in O_2 max reducedVAT by an average of 20%, whereas those who did not increaseO_2 max decreased VAT by only 10%,despite comparable reductions in body fat, fat mass, and subcutaneousadipose tissue area. The decrease in VAT was independently related tothe change in O_2 max(r² = 0.22; P < 0.01) andfat mass (r² = 0.08; P = 0.05). These data indicate that greater improvements inO_2 max with weight loss and walking areassociated with greater reductions in visceral adiposity in obesepostmenopausal women.

     

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.

     

Protective effects of intravascular pressure and nitric oxide in ischemic lung injury

Cessation of bloodflow during ischemia will decrease both distending and shearforces exerted on endothelium and may worsen ischemic lung injury bydecreasing production of nitric oxide (NO), which influences vascularbarrier function. We hypothesized that increased intravascular pressure(Piv) during ventilated ischemia might maintain NO productionby increasing endothelial stretch or shear forces, thereby attenuatingischemic lung injury. Injury was assessed by measuring the filtrationcoefficient(K_f) and theosmotic reflection coefficient for albumin(_alb) after 3 h of ventilated(95% O₂-5%CO₂; expiratory pressure 3 mmHg) ischemia. Lungs were flushed with physiological salt solution, and then Piv was adjusted to achieve High Piv (mean 6.7 ± 0.4 mmHg, n = 15) or Low Piv (mean0.83 ± 0.4 mmHg, n = 10).N^G-nitro-L-arginine methyl ester(L-NAME;10⁵ M,n = 10),N^G-nitro-D-argininemethyl ester (D-NAME;10⁵ M,n = 11), orL-NAME(10⁵M)+L-arginine (5 × 10⁴ M,n = 6) was added at the start ofischemia in three additional groups of lungs with High Piv.High Piv attenuated ischemic injury compared with Low Piv(_alb 0.67 ± 0.04 vs. 0.35 ± 0.04, P < 0.05). Theprotective effect of High Piv was abolished byL-NAME(_alb 0.37 ± 0.04, P < 0.05) but not byD-NAME(_alb 0.63 ± 0.07). The effects of L-NAME were overcomeby an excess of L-arginine(_alb 0.56 ± 0.05, P < 0.05).K_f did not differsignificantly among groups. These results suggest that Piv modulatesischemia-induced barrier dysfunction in the lung, and theseeffects may be mediated by NO.

     

Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise

Barstow, Thomas J., Andrew M. Jones, Paul H. Nguyen, andRichard Casaburi. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise.J. Appl. Physiol. 81(4):1642-1650, 1996.We tested the hypothesis that the amplitude ofthe additional slow component ofO₂ uptake(O₂) during heavy exerciseis correlated with the percentage of type II (fast-twitch) fibers inthe contracting muscles. Ten subjects performed transitions to a workrate calculated to require aO₂ equal to 50% betweenthe estimated lactate (Lac) threshold and maximalO₂ (50%).Nine subjects consented to a muscle biopsy of the vastus lateralis. Toenhance the influence of differences in fiber type among subjects,transitions were made while subjects were pedaling at 45, 60, 75, and90 rpm in different trials. Baseline O₂ was designed to besimilar at the different pedal rates by adjusting baseline work ratewhile the absolute increase in work rate above the baseline was thesame. The O₂ response after the onset of exercise was described by a three-exponential model. Therelative magnitude of the slow component at the end of 8-min exercisewas significantly negatively correlated with %type I fibers at everypedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore,the gain of the fast component forO₂ (asml ^· min^{1 ·} W¹)was positively correlated with the %type I fibers across pedal rates(r = 0.69-0.83). Increase inpedal rate was associated with decreased relative stress of theexercise but did not affect the relationships between%fiber type and O₂parameters. The relative contribution of the slow component was alsosignificantly negatively correlated with maximalO₂(r = 0.65), whereas the gainfor the fast component was positively associated(r = 0.68-0.71 across rpm). Theamplitude of the slow component was significantly correlated with netend-exercise Lac at all four pedal rates(r = 0.64-0.84), but Lac was notcorrelated with %type I (P > 0.05).We conclude that fiber type distribution significantly affects both thefast and slow components ofO₂ during heavy exerciseand that fiber type and fitness may have both codependent andindependent influences on the metabolic and gas-exchange responses toheavy exercise.

     

Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus solitarii of conscious rats

This study aimedto determine the role of protein kinase C (PKC) in signal transductionmechanisms underlying ventilatory regulation in the nucleus tractussolitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate intothe commissural NTS of nine chronically instrumented, unrestrained ratselicited significant cardiorespiratory enhancements that lasted for atleast 4 h, whereas administration of vehicle(n = 15) or the inactive phorbol ester 4-phorbol 12,13-didecanoate (n = 7)did not elicit minute ventilation (E)changes. Peak hypoxic Eresponses (10% O₂-balanceN₂) were measured in 19 additional animals after NTS microinjection of bisindolylmaleimide(BIM) I, a selective PKC inhibitor (n = 12), BIM V (inactive analog; n = 7),or vehicle (Con; n = 19). In Con,E increased from 139 ± 9 to 285 ± 26 ml/min in room air and hypoxia, respectively, and similarresponses occurred after BIM V. BIM I did not affect room airE but markedly attenuated hypoxia-induced E increases (128 ± 12 to 167 ± 18 ml/min; P < 0.02 vs. Con and BIM V). When BIM I was microinjected into the cerebellum(n = 4), cortex(n = 4), or spinal cord(n = 4),E responses were similar to Con.Western blots of subcellular fractions of dorsocaudal brain stemlysates revealed translocation of PKC, , , , , and  isoenzymes during acute hypoxia, and enhanced overall PKC activity wasconfirmed in the particulate fraction of dorsocaudal brain stem lysatesharvested after acute hypoxia. These studies suggest that, in the adultrat, PKC activation in the NTS mediates essential components of theacute hypoxic ventilatory response.

     

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.

     

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.

     

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.

     

Testosterone and cortisol in relationship to dietary nutrients and resistance exercise

Volek, Jeff S., William J. Kraemer, Jill A. Bush, ThomasIncledon, and Mark Boetes. Testosterone and cortisol inrelationship to dietary nutrients and resistance exercise.J. Appl. Physiol. 82(1): 49-54, 1997.Manipulation of resistance exercise variables (i.e., intensity,volume, and rest periods) affects the endocrine response to exercise;however, the influence of dietary nutrients on basal andexercise-induced concentrations of hormones is less understood. Thepresent study examined the relationship between dietary nutrients andresting and exercise-induced blood concentrations of testosterone (T)and cortisol (C). Twelve men performed a bench press exercise protocol(5 sets to failure using a 10-repetitions maximum load) and a jumpsquat protocol (5 sets of 10 repetitions using 30% of each subject's1-repetition maximum squat) with 2 min of rest between all sets. Ablood sample was obtained at preexercise and 5 min postexercise fordetermination of serum T and C. Subjects also completed detaileddietary food records for a total of 17 days. There was a significant(P  0.05) increase in postexercise Tcompared with preexercise values for both the bench press (7.4%) andjump squat (15.1%) protocols; however, C was not significantly different from preexercise concentrations. Significantcorrelations were observed between preexercise T and percent energyprotein (r = 0.71), percentenergy fat (r = 0.72), saturated fattyacids (g ^· 1,000 kcal^{1 ·} day¹;r = 0.77), monounsaturated fatty acids(g ^· 1,000 kcal^{1 ·} day¹;r = 0.79), the polyunsaturatedfat-to-saturated fat ratio (r = 0.63), and the protein-to-carbohydrate ratio (r = 0.59). There were nosignificant correlations observed between any nutritional variables andpreexercise C or the absolute increase in T and C after exercise. Thesedata confirm that high-intensity resistance exercise results inelevated postexercise T concentrations. A more impressive finding wasthat dietary nutrients may be capable of modulating restingconcentrations of T.