Age alters the cardiovascular response to direct passive heating

Duringdirect passive heating in young men, a dramatic increase in skin bloodflow is achieved by a rise in cardiac output (_c) andredistribution of flow from the splanchnic and renal vascular beds. Toexamine the effect of age on these responses, seven young (Y; 23 ± 1 yr) and seven older (O; 70 ± 3 yr) men were passively heated withwater-perfused suits to their individual limit of thermal tolerance.Measurements included heart rate (HR), _c (byacetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (byp-aminohippurateclearance), and esophageal and mean skin temperatures._c wassignificantly lower in the older than in the young men (11.1 ± 0.7 and 7.4 ± 0.2 l/min in Y and O, respectively, at the limit ofthermal tolerance; P < 0.05),despite similar increases in esophageal and mean skin temperatures andtime to reach the limit of thermal tolerance. A lower stroke volume (99 ± 7 and 68 ± 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to anattenuated increase in inotropic function during heating, was theprimary factor for the lower _c observed inthe older men. Increases in HR were similar in the young and older men;however, when expressed as a percentage of maximal HR, the older menrelied on a greater proportion of their chronotropic reserve to obtainthe same HR response (62 ± 3 and 75 ± 4% maximal HR in Y andO, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from thecombined splanchnic and renal circulations at the limit of thermaltolerance (960 ± 80 and 720 ± 100 ml/min in Y and O,respectively, P < 0.05). As a resultof these combined attenuated responses, the older men had asignificantly lower increase in total blood flow directed to the skin.

     

Energy requirements and physical activity in free-living older women and men: a doubly labeled water study

Determinants of daily energy needs and physicalactivity are unknown in free-living elderly. This study examineddeterminants of daily total energy expenditure (TEE) andfree-living physical activity in older women(n = 51; age = 67 ± 6 yr) and men(n = 48; age = 70 ± 7 yr) by usingdoubly labeled water and indirect calorimetry. Usingmultiple-regression analyses, we predicted TEE by using anthropometric,physiological, and physical activity indexes. Data were collected onresting metabolic rate (RMR), body composition, peak oxygen consumption(O_{2 peak}),leisure time activity, and plasma thyroid hormone. Data adjusted forbody composition were not different between older women and men,respectively (in kcal/day): TEE, 2,306 ± 647 vs. 2,456 ± 666;RMR, 1,463 ± 244 vs. 1,378 ± 249; and physical activity energyexpenditure, 612 ± 570 vs. 832 ± 581. In a subgroup of 70 womenand men, RMR andO_{2 peak}explained approximately two-thirds of the variance in TEE(R² = 0.62;standard error of the estimate = ±348 kcal/day). Crossvalidation ofthis equation in the remaining 29 women and men was successful, with nodifference between predicted and measured TEE (2,364 ± 398 and2,406 ± 571 kcal/day, respectively). The strongest predictors ofphysical activity energy expenditure(P < 0.05) for womenand men were O_{2 peak}(r = 0.43), fat-free mass(r = 0.39), and body mass(r = 0.34). In summary, RMR andO_{2 peak} are importantindependent predictors of energy requirements in the elderly.Furthermore, cardiovascular fitness and fat-free mass are moderatepredictors of physical activity in free-living elderly.

     

Muscle quality. II. Effects of strength training in 65-to 75-yr-old men and women

To determine theeffects of strength training (ST) on muscle quality (MQ,strength/muscle volume of the trained muscle group), 12 healthy oldermen (69 ± 3 yr, range 65-75 yr) and 11 healthy older women (68 ± 3 yr, range 65-73 yr) were studied before and after aunilateral leg ST program. After a warm-up set, four sets ofheavy-resistance knee extensor ST exercise were performed 3 days/wk for9 wk on the Keiser K-300 leg extension machine. The men exhibitedgreater absolute increases in the knee extension one-repetition maximum(1-RM) strength test (75 ± 2 and 94 ± 3 kg before andafter training, respectively) and in quadriceps muscle volume measuredby magnetic resonance imaging (1,753 ± 44 and 1,955 ± 43 cm³) than the women (42 ± 2 and 55 ± 3 kg for the 1-RM test and 1,125 ± 53 vs.1,261 ± 65 cm³ forquadriceps muscle volume before and after training, respectively, inwomen; both P < 0.05). However,percent increases were similar for men and women in the 1-RM test (27 and 29% for men and women, respectively), muscle volume (12% forboth), and MQ (14 and 16% for men and women, respectively).Significant increases in MQ were observed in both groups in the trainedleg (both P < 0.05) and in the 1-RMtest for the untrained leg (both P < 0.05), but no significant differences were observed between groups,suggesting neuromuscular adaptations in both gender groups. Thus,although older men appear to have a greater capacity for absolutestrength and muscle mass gains than older women in response to ST, the relative contribution of neuromuscular and hypertrophic factors to theincrease in strength appears to be similar between genders.

     

Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation

Jensen, Michael D., Tu T. Nguyen, A. HernándezMijares, C. Michael Johnson, and Michael J. Murray. Effects ofgender on resting leg blood flow: implications for measurement ofregional substrate oxidation. J. Appl.Physiol. 84(1): 141-145, 1998.These studies weredesigned to examine whether the respiratory quotient (RQ) of leg tissue(primarily skeletal muscle) would increase to a greater degree in womenthan in men during meal ingestion. We found that mean leg and systemicRQ values were similar in men under both basal and fed conditions,whereas the agreement was poor in women. In women, leg RQ values tendedto be greater than the systemic RQ, whereas splanchnic RQ values tendedto be lower than the systemic RQ. The possibility that measurementimprecision accounted for the different findings in women could not beexcluded because the arteriovenous bloodO₂ differences were almost twice as great in men as in women (53.7 ± 5.4 vs. 28.6 ± 2.9 ml ofO₂/l, respectively;P < 0.01), as were venoarterialblood CO₂ differences. The smallerarteriovenous differences in women appeared to limit our ability toaccurately measure their leg RQ values.O₂ uptake relative to leg fat-freemass (FFM) was not different between men and women, whereas leg bloodflow relative to leg FFM was greater in women than in men (55 ± 3vs. 39 ± 2 ml · kgFFM¹ · min¹,respectively; P < 0.001). Thesefindings were confirmed by examining data from other studies conductedin our laboratory to create a larger data set. We conclude that restingleg blood flow in women is greater (relative to FFM) than in men,making it more difficult to accurately measure leg RQ in women.

     

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

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

     

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.

     

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.

     

Regional deposition of inhaled particles in human lungs: comparison between men and women

We measured detailed regional depositionpatterns of inhaled particles in healthy adult male(n = 11; 25 ± 4 yr of age) and female (n = 11; 25 ± 3 yr of age)subjects by means of a serial bolus aerosol delivery technique formonodisperse fine [particle diameter(D_p) = 1 µm] and coarse aerosols(D_p = 3 and 5 µm). The bolus aerosol (40 ml half-width) was delivered to a specificvolumetric depth (Vp) of the lung ranging from 100 to 500 ml with a50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp,showing characteristic unimodal curves with respect to particle sizeand flow rate. However, the unevenness was more pronounced in women.LDF tended to be greater in all regions of the lung in women than inmen for D_p = 1 µm. For D_p = 3 and 5 µm, LDF showed a marked enhancement in the shallow region of Vp  200 ml in women compared with men(P < 0.05). LDF in women wascomparable to or smaller than those of men in deep lung regions of Vp > 200 ml. Total lung deposition was comparable between men and womenfor fine particles but was consistently greater in women than men forcoarse particles regardless of flow rates used: the difference rangedfrom 9 to 31% and was greater with higher flow rates(P < 0.05). The results indicatethat 1) particledeposition characteristics differ between healthy men and women undercontrolled breathing conditions and2) deposition in women is greaterthan that in men.

     

Amiloride-sensitive sodium current in everted Ambystoma initial collecting tubule: short-term insulin effects

Whole cellpatch-clamp techniques were used to investigate amiloride-sensitivesodium conductance (G_Na) in the everted initial collecting tubule of Ambystoma. Accessibility to both theapical and basolateral membranes made this preparation ideal forstudying the regulation of sodium transport by insulin.G_Na accounted for 20% of total cell conductance(G_T) under control conditions. A restingmembrane potential of 75 ± 2 mV (n = 7)together with the fact that G_T is stable withtime suggested that the cells studied were viable. Measurements ofcapacitance and use of a known uncoupling agent, heptanol, suggestedthat cells were not electrically coupled. Thus the values ofG_T and G_Na represented individual principal cells. Exposure of the basolateral membrane toinsulin (1 mU/ml) for 10-60 min significantly (P < 0.05) increased the normalized G_Na [1.2 ± 0.3 nS (n = 6) vs. 2.0 ± 0.4 nS(n = 6)]. Cell-attached patch-clamp techniques wereused to further elucidate the mechanism by which insulin increasesamiloride-sensitive epithelial sodium channel (ENaC) activity. In thepresence of insulin there was no apparent change in either the numberof active levels/patch or the conductance of ENaC. The openprobability increased significantly (P < 0.01) from0.21 ± 0.04 (n = 6) to 0.46 ± 0.07 (n = 6). Thus application of insulin enhanced sodium reabsorption by increasing the fraction of time the channel spent inthe open state.

     

Thermal and metabolic responses to cold-water immersion at knee, hip, and shoulder levels

Lee, Dae T., Michael M. Toner, William D. McArdle, IoannisS. Vrabas, and Kent B. Pandolf. Thermal and metabolic responses tocold-water immersion at knee, hip, and shoulder levels.J. Appl. Physiol. 82(5):1523-1530, 1997.To examine the effect of cold-water immersion atdifferent depths on thermal and metabolic responses, eight men (25 yrold, 16% body fat) attempted 12 tests: immersed to the knee (K), hip(H), and shoulder (Sh) in 15 and 25°C water during both rest (R) orleg cycling [35% peak oxygen uptake; (E)] for up to 135 min. At 15°C, rectal (T_re)and esophageal temperatures(T_es) between R and E were notdifferent in Sh and H groups (P > 0.05), whereas both in K group were higher during E than R(P < 0.05). At 25°C,T_re was higher(P < 0.05) during E than R at alldepths, whereas T_es during E washigher than during R in H and K groups.T_re remained at control levels inK-E at 15°C, K-E at 25°C, and in H-E groups at 25°C,whereas T_es remained unchanged inK-E at 15°C, in K-R at 15°C, and in all 25°C conditions (P > 0.05). During R and E, themagnitude of T_re change wasgreater (P < 0.05) than themagnitude of T_es change in Sh andH groups, whereas it was not different in the K group(P > 0.05). Total heat flow wasprogressive with water depth. During R at 15 and 25°C, heatproduction was not increased in K and H groups from control level(P > 0.05) but it did increase in Shgroup (P < 0.05). The increase inheat production during E compared with R was smaller(P < 0.05) in Sh (121 ± 7 W/m² at 15°C and 97 ± 6 W/m² at 25°C) than in H (156 ± 6 and 126 ± 5 W/m²,respectively) and K groups (155 ± 4 and 165 ± 6 W/m², respectively). These datasuggest that T_re andT_es respond differently duringpartial cold-water immersion. In addition, water levels above knee in15°C and above hip in 25°C cause depression of internal temperatures mainly due to insufficient heat production offsetting heatloss even during light exercise.

     

Angiogenic growth factor mRNA responses to passive and contraction-induced hyperperfusion in skeletal muscle

It has been proposed that, in skeletal muscle,the angiogenic response to exercise may be signaled by the increase inmuscle blood flow, via biomechanical changes in the microcirculation (increased shear stress and/or wall tension). Toexamine this hypothesis, we compared the change in abundance ofvascular endothelial growth factor (VEGF), basic fibroblast growthfactor (bFGF), and transforming growthfactor-₁(TGF-₁) mRNA in skeletalmuscles of the canine leg after 1 h of pump-controlled high blood flow alone (passive hyperperfusion; protocolA) and electrical stimulation of the femoral andsciatic nerves producing muscle contraction (protocolB). The increase in leg blood flow (5.4- and 5.9-fold change from resting values, respectively) was similar in both groups.Passive hyperperfusion alone did not increase message abundance forVEGF (ratio of mRNA to 18S signals after vs. before hyperperfusion,0.94 ± 0.08) or bFGF (1.08 ± 0.05) but slightly increased thatof TGF-₁ (1.14 ± 0.07;P < 0.03). In contrast, aspreviously found in the rat, electrical stimulation provoked more thana threefold increase in VEGF mRNA abundance (3.40 ± 1.45;P < 0.02). However, electricalstimulation produced no significant changes in either bFGF (1.16 ± 0.13) or TGF-₁ (1.31 ± 0.27). These results suggest that the increased muscle blood flow of exercise does not account for the increased abundance of these angiogenic growth factor mRNA levels in response to acuteexercise. We speculate that other factors, such as localhypoxia, metabolite concentration changes, or mechanical effects ofcontraction per se, may be responsible for the effects of exercise.

     

Dynamics of segmental extracellular volumes during changes in body position by bioimpedance analysis

Extracellularvolume (ECV) of arms, trunk, and legs determined from segmentalbioimpedance data in 11 healthy men (31.6 ± 7 yr) obtained at theend of a 30-min equilibration phase in the supine body position wascompared with ECV determined from whole body measurements(ECV_WB). ECV was calculated fromextracellular resistance(R_ECV)identified from the bioimpedance spectrum for a range of 10 frequencies. Whole bodyR_ECV (527.6 ± 55.6 ) was equal to the sum ofR_ECV in the arms,trunk, and legs (241.6 ± 36.3, 49.2 ± 5.1, and 236.3 ± 25.5 , respectively). The sum of equilibrated ECV in arms (1.31 ± 0.25 liters), trunk (10.08 ± 1.65 liters), and legs (2.80 ± 0.82 liters) was smaller thanECV_WB (20.90 ± 2.59 liters).In six subjects who changed from a standing to a supine body position,ECV decreased in arms (2.59 ± 2.51%, P = NS) and legs (10.96 ± 3.02%, P < 0.05) but increased inthe trunk (+4.2 ± 3.2%, P < 0.05). ECV_WB also decreased(4.98 ± 1.41%, P < 0.05). However, the sum of segmental extracellular volumes remainedunchanged (0.06 ± 0.07%, P = NS). The sum of segmental ECVs is not sensitive to changes in bodyposition, which otherwise interferes with the estimation of ECV inbioimpedance analysis when ECV_WBis used.

     

Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise

We have recently demonstrated that changes inthe work of breathing during maximal exercise affect leg blood flow andleg vascular conductance (C. A. Harms, M. A. Babcock, S. R. McClaran, D. F. Pegelow, G. A. Nickele, W. B. Nelson, and J. A. Dempsey. J. Appl. Physiol. 82: 1573-1583,1997). Our present study examined the effects of changesin the work of breathing on cardiac output (CO) during maximalexercise. Eight male cyclists [maximalO₂ consumption(O_{2 max}):62 ± 5 ml · kg¹ · min¹]performed repeated 2.5-min bouts of cycle exercise atO_{2 max}. Inspiratorymuscle work was either 1) at controllevels [inspiratory esophageal pressure (Pes): 27.8 ± 0.6 cmH₂O],2) reduced via a proportional-assistventilator (Pes: 16.3 ± 0.5 cmH₂O), or 3) increased via resistive loads(Pes: 35.6 ± 0.8 cmH₂O).O₂ contents measured in arterialand mixed venous blood were used to calculate CO via the direct Fickmethod. Stroke volume, CO, and pulmonaryO₂ consumption(O₂) were not different(P > 0.05) between control andloaded trials atO_{2 max} but were lower(8, 9, and 7%, respectively) than control withinspiratory muscle unloading atO_{2 max}. Thearterial-mixed venous O₂difference was unchanged with unloading or loading. We combined thesefindings with our recent study to show that the respiratory muscle work normally expended during maximal exercise has two significant effectson the cardiovascular system: 1) upto 14-16% of the CO is directed to the respiratory muscles; and2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles.

     

Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo

Brown, Robert H., Wayne Mitzner, and Elizabeth M. Wagner.Interaction between airway edema and lung inflation onresponsiveness of individual airways in vivo. J. Appl.Physiol. 83(2): 366-370, 1997.Inflammatorychanges and airway wall thickening are suggested to cause increasedairway responsiveness in patients with asthma. In fivesheep, the dose-response relationships of individual airways weremeasured at different lung volumes to methacholine (MCh) before andafter wall thickening caused by the inflammatory mediator bradykininvia the bronchial artery. At 4 cmH₂O transpulmonary pressure(Ptp), 5 µg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH₂O Ptp, MCh resultedin less constriction (to 31 ± 5%). Bradykinin increased airwaywall area at 4 and 30 cmH₂O Ptp(159 ± 6 and 152 ± 4%, respectively;P < 0.0001). At 4 cmH₂O Ptp, bradykinin decreasedairway luminal area (13 ± 2%; P < 0.01), and the dose-response curve was significantly lower (P = 0.02). At 30 cmH₂O, postbradykinin, the maximalairway narrowing was not significantly different (26 ± 5%;P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation ofthe MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effecton the MCh-induced airway constriction. We conclude that inflammatoryfluid leakage in the airways cannot be a primary cause of airwayhyperresponsiveness.

     

Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat: putative role of nitric oxide

In humans, the hypoxic ventilatory response(HVR) is augmented when preceded by a short hyperoxic exposure (Y. Honda, H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. J. Appl.Physiol. 81: 1627-1632, 1996). To examine whetherneuronal nitric oxide synthase (nNOS) is involved in such hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult ratsunderwent hypoxic challenges (10%O₂-5%CO₂-balanceN₂) preceded either by 10 min ofroom air (O₂) or of 100%O₂(+O₂). At least 48 h later,similar challenges were performed after the animals received theselective nNOS inhibitor 7-nitroindazole (25 mg/kg ip). InO₂ runs, minute ventilation(E)increased from 121.3 ± 20.5 (SD) ml/min in room air to 191.7 ± 23.8 ml/min in hypoxia (P < 0.01). After +O₂,E increasedfrom 114.1 ± 19.8 ml/min in room air to 218.4 ± 47.0 ml/min inhypoxia (+O₂ vs.O₂:P < 0.005, ANOVA). After7-nitroindazole administration, HVR was not affected in theO₂ treatment group withE increasingfrom 113.7 ± 17.8 ml/min in room air to 185.8 ± 35.0 ml/min inhypoxia (P < 0.01).However, HVR potentiation in+O₂-exposed animals was abolished(111.8 ± 18.0 ml/min in room air to 184.1 ± 35.6 ml/min inhypoxia; +O₂ vs.O₂:P not significant). We conclude that in the conscious rat nNOS activation mediates essential components ofthe HVR potentiation elicited by a previous short hyperoxic exposure.

     

Luminal L-alanine stimulates exocytosis at the K+-conductive apical membrane of Aplysia enterocytes

In Aplysia intestine,stimulation of Na⁺ absorption withluminal alanine increases apical membraneK⁺ conductance(G_K,a), whichpresumably regulates enterocyte volume during stimulatedNa⁺ absorption. However, themechanism responsible for the sustained increase in plasma membraneK⁺ conductance is not known forany nutrient-absorbing epithelium. In the present study, we have begunto test the hypothesis that the alanine-induced increase inG_K,a inAplysia enterocytes results fromexocytic insertion of K⁺ channelsinto the apical membrane. We used the fluid-phase marker horseradishperoxidase to assess the effect of alanine on apical membraneexocytosis and conventional microelectrode techniques to assess theeffect of alanine on fractional capacitance of the apical membrane(fC_a). Luminalalanine significantly increased apical membrane exocytosis from 1.04 ± 0.30 to 1.39 ± 0.38 ng · min¹ · cm².To measure fC_a,we modeled the Aplysia enterocyte as adouble resistance-capacitance (RC) electric circuit arranged in series. Several criteria were tested to confirm application of the model to theenterocytes, and all satisfied the model. When added to the luminalsurface, alanine significantly increasedfC_a from 0.27 ± 0.02 to 0.33 ± 0.04 (n = 10)after 4 min. There are two possible explanations for our findings:1) the increase in exocytosis, whichadds membrane to the apical plasma membrane, prevents plasma membranefracture, and 2) the increase inexocytosis delivers K⁺ channels tothe apical membrane by exocytic insertion. After the alanine-induceddepolarization of apical membrane potential (V_a), there isa strong correlation (r = 0.96)between repolarization ofV_a, whichreflects the increase inG_K,a, andincrease in fC_a. This correlation supports the exocytic insertion hypothesis for activation ofG_K,a.

     

Thermal and circulatory responses during exercise: effects of hypohydration, dehydration, and water intake

Armstrong, Lawrence E., Carl M. Maresh, Catherine V. Gabaree, Jay R. Hoffman, Stavros A. Kavouras, Robert W. Kenefick, JohnW. Castellani, and Lynn E. Ahlquist. Thermal and circulatory responses during exercise: effects of hypohydration, dehydration, andwater intake. J. Appl. Physiol. 82(6):2028-2035, 1997.This investigation examined the distinct andinteractive effects of initial hydration state, exercise-induceddehydration, and water rehydration in a hot environment. On fouroccasions, 10 men performed a 90-min heat stress test (treadmillwalking at 5.6 km/h, 5% grade, 33°C, 56% relative humidity).These heat stress tests differed in pretest hydration [2euhydrated (EU) and 2 hypohydrated (HY) trials] and water intakeduring exercise [2 water ad libitum (W) and 2 no water (NW)trials]. HY + NW indicated greater physiological strain than allother trials (P < 0.05-0.001)in heart rate, plasma osmolality(P_osm), sweat sensitivity(g / °C · min), and rectal temperature.Unexpectedly, final HY + W and EU + W responses for rectal temperature,heart rate, and P_osm were similar,despite the initial 3.9 ± 0.2% hypohydration in HY + W. Weconcluded that differences in pretestP_osm (295 ± 7 and 287 ± 5 mosmol/kg for HY + W and EU + W, respectively) resulted in greaterwater consumption (1.65 and 0.31 liter for HY + W and EU + W,respectively), no voluntary dehydration (0.9% body mass increase), andattenuated thermal and circulatory strain during HY + W.

     

Cerebral vasomotor reactivity at high altitude in humans

The purpose of this study was twofold:1) to determine whether at highaltitude cerebral blood flow (CBF) as assessed during CO₂ inhalation and duringhyperventilation in subjects with acute mountain sickness (AMS) wasdifferent from that in subjects without AMS and2) to compare the CBF as assessedunder similar conditions in Sherpas at high altitude and in subjects atsea level. Resting control values of blood flow velocity in themiddle cerebral artery (V_MCA), pulseoxygen saturation (Sa_O2), andtranscutaneous PCO₂ were measured at4,243 m in 43 subjects without AMS, 17 subjects with AMS, 20 Sherpas,and 13 subjects at sea level. Responses ofCO₂ inhalation andhyperventilation onV_MCA,Sa_O2, and transcutaneous PCO₂ were measured, and the cerebralvasomotor reactivity (VMR = V_MCA/PCO₂)was calculated as the fractional change ofV_MCA per Torrchange of PCO₂, yielding ahypercapnic VMR and a hypocapnic VMR. AMS subjects showeda significantly higher resting controlV_MCA than didno-AMS subjects (74 ± 22 and 56 ± 14 cm/s, respectively;P < 0.001), andSa_O2 was significantly lower (80 ± 8 and 88 ± 3%, respectively; P < 0.001). Resting control V_MCA values inthe sea-level group (60 ± 15 cm/s), in the no-AMS group, and inSherpas (59 ± 13 cm/s) were not different. Hypercapnic VMR valuesin AMS subjects were 4.0 ± 4.4, in no-AMS subjects were 5.5 ± 4.3, in Sherpas were 5.6 ± 4.1, and in sea-level subjects were 5.6 ± 2.5 (not significant). Hypocapnic VMR values were significantly higher in AMS subjects (5.9 ± 1.5) compared with no-AMS subjects (4.8 ± 1.4; P < 0.005) but werenot significantly different between Sherpas (3.8 ± 1.1) and thesea-level group (2.8 ± 0.7). We conclude that AMS subjects havegreater cerebral hemodynamic responses to hyperventilation, higherV_MCAresting control values, and lower Sa_O2 compared with no-AMSsubjects. Sherpas showed a cerebral hemodynamic patternsimilar to that of normal subjects at sea level.     

Lung resistance and elastance in spontaneously breathing preterm infants: effects of breathing pattern and demographics

Reported values of lung resistance(RL) and elastance (EL) in spontaneouslybreathing preterm neonates vary widely. We hypothesized that thisvariability in lung properties can be largely explained by both inter-and intrasubject variability in breathing pattern and demographics.Thirty-three neonates receiving nasal continuous positive airwaypressure [weight 606-1,792 g, gestational age (GA) of25-33 wk, 2-49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by facemask pneumotachography. Breath-to-breath changes in RL andEL in each infant were estimated by Fourier analysis ofimpedance (Z) and by multiple linear regression (MLR).RL_MLR (RL_MLR = 0.85 × RL_Z 0.43; r² = 0.95) and EL_MLR(EL_MLR = 0.97 × EL_Z + 8.4; r² = 0.98) werehighly correlated to RL_Z andEL_Z, respectively. Both RL(mean ± SD; RL_Z = 70 ± 38, RL_MLR = 59 ± 36 cmH₂O · s · l¹)and EL (EL_Z = 434 ± 212, EL_MLR = 436 ± 210 cmH₂O/l)exhibited wide intra- and intersubject variability.Regardless of computation method, RL was found to decreaseas a function of weight, age, respiratory rate (RR), and tidal volume(VT) whereas it increased as a function ofRR · VT and inspiratory-to-expiratorytime ratio (TI/TE). EL decreasedwith increasing weight, age, VT and female gender andincreased as RR and TI/TE increased. Weconclude that accounting for the effects of breathing patternvariability and demographic parameters on estimates of RLand EL is essential if they are to be of clinical value.Multivariate statistical models of RL and ELmay facilitate the interpretation of lung mechanics measurements inspontaneously breathing infants.

     

Regulation of the epithelial Na(+) channel by extracellular acidification

The effect of extracellular acidification wastested on the native epithelial Na⁺ channel (ENaC) in A6epithelia and on the cloned ENaC expressed in Xenopusoocytes. Channel activity was determined utilizing blocker-inducedfluctuation analysis in A6 epithelia and dual electrode voltage clampin oocytes. In A6 cells, a decrease of extracellular pH(pH_o) from 7.4 to 6.4 caused a slow stimulation of theamiloride-sensitive short-circuit current (I_Na)by 68.4 ± 11% (n = 9) at 60 min. This increaseof I_Na was attributed to an increase of openchannel and total channel (N_T) densities. Similar changes were observed with pH_o 5.4. The effects ofpH_o were blocked by buffering intracellularCa²⁺ with 5 µM1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Inoocytes, pH_o 6.4 elicited a small transient increase of theslope conductance of the cloned ENaC (11.4 ± 2.2% at 2 min)followed by a decrease to 83.7 ± 11.7% of control at 60 min (n = 6). Thus small decreases of pH_ostimulate the native ENaC by increasing N_T butdo not appreciably affect ENaC expressed in Xenopus oocytes.These effects are distinct from those observed with decreasingintracellular pH with permeant buffers that are known to inhibit ENaC.