Short- and long-term effects of testosterone on diaphragm in castrated and normal male rats

Prezant, David J., Manoj L. Karwa, Helen H. Kim, DianeMaggiore, Virginia Chung, and David E. Valentine. Short- and long-term effects of testosterone on diaphragm in castrated and normalmale rats. J. Appl. Physiol. 82(1):134-143, 1997.The effects of short- and long-term testosteroneabsence or treatment on the diaphragm were studied in castrated andsexually normal male rats. Compared with control rats (untreated normalmales), testosterone absence or treatment did not significantly affect costal weight. In untreated castrated males, there were significant decreases in specific forces, type II fiber cross-sectional area, andmyosin heavy chain (MHC) isoform 2B after 2.5 wk. In castrated malesthat received testosterone, there were significant increases inspecific forces, type II total fiber proportional area, and relativeexpression of all adult diaphragm fast MHC isoforms(MHC-2_all) after 2.5 wk. In normal males thatreceived testosterone, the only significant finding was an increase inMHC-2B after 2.5 wk. Across all groups, there was close correlationbetween increases in maximum tetanic forces and MHC-2_all.Changes in diaphragm function and composition were closely related tochanges in serum testosterone levels at 2.5 wk. The lack of significantchange in diaphragm function at 10 wk occurred despite changes in serumtestosterone levels and diaphragm composition similar to those at 2.5 wk. These findings support our hypothesis that the effects oftestosterone are dependent on basal circulating androgen levels andstudy duration.

     

Modulation of MHC isoforms in functionally overloaded and exercised rat plantaris fibers

Roy, Roland R., Robert J. Talmadge, Kenneth Fox, MichaelLee, Aki Ishihara, and V. Reggie Edgerton. Modulation of MHC isoforms in functionally overloaded and exercised rat plantaris fibers.J. Appl. Physiol. 83(1): 280-290, 1997.The effects of 1 and 10 wk of functional overload (FO) of therat plantaris with (FO_Tr) andwithout daily endurance treadmill training on its myosin heavy chain(MHC) composition were studied. After 1 and 10 wk of FO, plantaris masswas 22 and 56% greater in FO and 37 and 94% greater, respectively, inFO_Tr rats compared withage-matched controls. At 1 wk, pure type I and pure type IIa MHC fiberswere hypertrophied in FO (39 and 44%) andFO_Tr (70 and 87%) rats. By 10 wkall fiber types comprising >5% of the fibers sampled showed ahypertrophic response in both FO groups. One week of FO increased thepercentage of hybrid (containing both type I and type IIa MHC) fibersand of fibers containing embryonic MHC. By 10 wk, the percentage ofpure type I MHC fibers was ~40% in both FO groups compared with 15%in controls, and the percentage of fibers containing embryonic MHC wassimilar to that in controls. Sodium dodecyl sulfate-polyacrylamide gelelectrophoresis analyses showed an increase in type I MHC and adecrease in type IIb MHC in both FO groups at 10 wk, whereas littlechange was observed at 1 wk. These data are consistent with hypertrophyand transformation from faster to slower MHC isoforms in chronicallyoverloaded muscles. The additional overload imposed by daily endurancetreadmill training employed in this study (1.6 km/day; 10% incline)results in a larger hypertrophic response but appears to have a minimaleffect on the MHC adaptations.

     

Enlargement of glycogen store in rat liver and muscle by fructose-diet intake and exercise training

Murakami, Taro, Yoshiharu Shimomura, Noriaki Fujitsuka,Masahiro Sokabe, Koji Okamura, and Shuichi Sakamoto. Enlargement of glycogen store in rat liver and muscle by fructose-diet intake andexercise training. J. Appl. Physiol.82(3): 772-775, 1997.This study investigated the effect oflong-term intake of a fructose diet and exercise training on glycogencontent in liver and skeletal muscle in female rats. Thirty-six rats (8 wk old) were divided into two dietary groups and were fed with acontrol (chow) diet or fructose diet (containing 20% fructose) for 12 wk. During this period, one-half of the rats in each dietary group weretrained by using a motor-driven treadmill (running speed of 25 m/minand duration of 90 min/day, 5 days/wk). The liver glycogen wasincreased by intake of a fructose diet and exercise training, and thecontent was in the following order: control-diet and sedentary rats < fructose-diet and sedentary rats  control-diet and trained rats < fructose-diet and trained rats in the ratio of 1:3.4:3.6:5.0. Theglycogen content in gastrocnemius muscle showed the same trend as thatin liver; the ratio was 1:1.3:1.3:1.6. These results indicate that bothlong-term intake of the fructose diet and exercise training synergistically increased glycogen in both tissues.

     

Exercise training improves lusitropy by isoproterenol in papillary muscles from aged rats

Taffet, George E., Lloyd A. Michael, and Charlotte A. Tate.Exercise training improves lusitropy by isoproterenol in papillarymuscles from aged rats. J. Appl.Physiol. 81(4): 1488-1494, 1996.Aging isassociated with a decreased cardiac responsiveness to -adrenergicstimulation. We examined the effect of endurance exercise training ofold Fischer 344 male rats on -adrenergic stimulation of the functionof isolated left ventricular papillary muscle. Three groups wereexamined: sedentary mature (SM; 12-mo old), sedentary old (SO;23-24 mo old), and exercised old (EO; 23-24 mo old) that weretreadmill trained for 4-8 wk. The isometric contractile propertieswere studied at 0.2 Hz and 0.75 mM calcium. Without -adrenergicstimulation, there were no group differences for peak tension, maximumrate of tension development(+dP/dt), or maximum rateof tension dissipation(dP/dt). The time to peak tension was longer (P < 0.05) forboth EO and SO than for SM rats. Half relaxation time(RT_1/2) was prolonged(P < 0.05) for SO compared with SMand EO (which did not differ). The three groups did not differ in the-adrenergic stimulation by isoproterenol of peak tension,dP/dt, time to peak tension, orcontraction duration. The inotropic response(+dP/dt) of SM was greater(P < 0.05) than that in SO or EOrats (which did not differ); however, the lusitropic response(RT_1/2) was lesser(P < 0.05) in SO than in SM or EO rats (which did not differ). Thus exercise training of old rats improved the lusitropic response to isoproterenol without altering theage-associated impairment in inotropic response.

     

Alterations in myocardial signal transduction due to aging and chronic dynamic exercise

Roth, David A., Cynthia D. White, Deborah A. Podolin, andRobert S. Mazzeo. Alterations in myocardial signal transduction due to aging and chronic dynamic exercise. J. Appl. Physiol.84(1): 177-184, 1998.Normal aging without disease leads todiminished chronotropic and inotropic responses to catecholaminestimulation, resulting in depressed cardiac function with stress. Thepurpose of this study was to determine molecular mechanisms fordecrements in adrenergic responsiveness of the left ventricle (LV) dueto aging and to study the effects of chronic dynamic exercise on signaltransduction. We measured -adrenergic receptor (-AR) density,adenylyl cyclase (AC) activity, and G-protein content and distributionin LV from 66 male Fischer 344 rats from three age groups that wereeither sedentary or treadmill trained (60 min/day, 5 days/wk, 10 wk at75% of the maximal capacity). Final ages were 7 mo(young), 15 mo (middle-age), and 25 mo (old). There was no significantdifference in -AR density among groups as a function of age ortraining. AC production of adenosine 3,5-cyclic monophosphate (cAMP)with the use of five pharmacological stimulations revealed that oldsedentary myocardium had depressed basal, receptor-dependent, G-protein-dependent, and AC catalyst stimulation (30-43%)compared with hearts from young and middle-age sedentary rats. Training did not alter AC activity in either middle-age or old groups but didincrease G-protein-dependent cAMP production in young myocardium (12-34%). Immunodetectable concentrations of stimulatory andinhibitory G proteins (G_s and G_i, respectively)showed 43% less total G_s with similar G_icontent in hearts from old sedentary compared with middle-age sedentaryrats. When compared with young sedentary animals, G_icontent was 39 and 50% higher in middle-age sedentary and oldsedentary myocardium, respectively. With age, there was a significantshift in the -subunit of G_s distribution from cytosolic fractions of LV homogenates to membrane-bound fractions (8-12% redistribution in middle-age sedentary vs. old sedentary). The mostsignificant training effect was a decrease in G_i content inhearts from old trained rats (23%), which resulted in values comparable with young sedentary rats and reduced theG_i/G_s ratio by 27% in old-rat LV. We reportthat age-associated reductions in cardiovascular -adrenergicresponsiveness correspond with alterations in postreceptor adrenergicsignaling rather than with a decrease in receptor number. Chronicdynamic exercise partially attenuates these reductions throughalterations in postreceptor elements of cardiac signal transduction.

     

Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart

Osborn, Brett A., June T. Daar, Richard A. Laddaga, Fred D. Romano, and Dennis J. Paulson. Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. J. Appl. Physiol. 82(3): 828-834, 1997.This study determined whether dynamic exercise training ofdiabetic rats would increase the expression of the GLUT-4 glucosetransport protein in prepared cardiac sarcolemmal membranes. Fourgroups were compared: sedentary control, sedentary diabetic, trainedcontrol, and trained diabetic. Diabetes was induced by intravenousstreptozotocin (60 mg/kg). Trained control and diabetic rats were runon a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk.Sarcolemmal membranes were isolated by using differentialcentrifugation, and the activity of sarcolemmalK⁺-p-nitrophenylphosphatase( pNPPase; an indicator ofNa⁺-K⁺-adenosinetriphosphataseactivity) was quantified. Hearts from the sedentary diabetic groupexhibited a significant depression of sarcolemmal pNPPaseactivity. Exercise training did not significantly alterpNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative tocontrol rats. In the trained diabetic animals, sarcolemmal GLUT-4protein levels were only reduced by 50% relative to control values,whereas GLUT-4 mRNA were returned to control levels. The increase inmyocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heartby enhancing myocardial glucose oxidation and cardiac performance

     

Effect of chronic resistive loading on hypoxic ventilatory responsiveness

Greenberg, Harly E., Rammohan S. Rao, Anthony L. Sica, andSteven M. Scharf. Effect of chronic resistive loading on hypoxicventilatory responsiveness. J. Appl.Physiol. 82(2): 500-507, 1997.Depression ofventilation mediated by endogenous opioids has been observed acutelyafter resistive airway loading. We evaluated the effects of chronicallyincreased airway resistance on hypoxic ventilatory responsivenessshortly after load imposition and 6 wk later. A circumferentialtracheal band was placed in 200-g rats, tripling tracheal resistance.Sham surgery was performed in controls. Ventilation and the ventilatoryresponse to hypoxia were measured by using barometric plethysmographyat 2 days and 6 wk postsurgery in unanesthetized rats during exposureto room air and to 12% O₂-5%CO₂-balanceN₂. Trials were performed with andwithout naloxone (1 mg/kg ip). Room air arterial blood gases demonstrated hypercapnia with normoxia in obstructed rats at 2 days and6 wk postsurgery. During hypoxia, a 30-Torr fall inPO₂ occurred with no change inPCO₂. Hypoxic ventilatory responsiveness was suppressed in obstructed rats at 2 days postloading. Naloxone partially reversed this suppression. However, hypoxic responsiveness at 6 wk was not different from control levels. Naloxonehad a small effect on ventilatory pattern at this time with no overalleffect on hypoxic responsiveness. This was in contrast to previouslydemonstrated long-term suppression ofCO₂ sensitivity in this model,which was partially reversible by naloxone only during the immediateperiod after load imposition. Endogenous opioids apparently modulateventilatory control acutely after load imposition. Their effect waneswith time despite persistence of depressedCO₂ sensitivity.

     

Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus)

Swallow, John G., Theodore Garland, Jr., Patrick A. Carter,Wen-Zhi Zhan, and Gary C. Sieck. Effects of voluntary activity andgenetic selection on aerobic capacity in house mice(Mus domesticus). J. Appl. Physiol. 84(1): 69-76, 1998.An animal model was developed to study effects on components ofexercise physiology of both "nature" (10 generations of geneticselection for high voluntary activity on running wheels) and"nurture" (7-8 wk of access or no access to running wheels,beginning at weaning). At the end of the experiment, mice from bothwheel-access groups were significantly lighter in body mass than micefrom sedentary groups. Within the wheel-access group, a statisticallysignificant, negative relationship existed between activity and finalbody mass. In measurements of maximum oxygen consumption during forcedtreadmill exercise (O_{2 max}), mice withwheel access were significantly more cooperative than sedentary mice;however, trial quality was not a significant predictor of individualvariation in O_{2 max}.Nested two-way analysis of covariance demonstrated that both geneticselection history and access to wheels had significant positive effects on O_{2 max}.A 12% difference inO_{2 max} existedbetween wheel-access selected mice, which had the highestmass-correctedO_{2 max}, andsedentary control mice, which had the lowest. The respiratory exchangeratio at O_{2 max} wasalso significantly lower in the wheel-access group. Our results suggestthe existence of a possible genetic correlation between voluntaryactivity levels (behavior) and aerobic capacity (physiology).

     

Mortality rate and longevity of food-restricted exercising male rats: a reevaluation

Holloszy, John O. Mortality rate and longevity offood-restricted exercising male rats: a reevaluation.J. Appl. Physiol. 82(2): 399-403, 1997.Food restriction increases the maximal longevity of rats. Malerats do not increase their food intake to compensate for the increasein energy expenditure in response to exercise. However, a decrease inthe availability of energy for growth and cell proliferation thatinduces an increase in maximal longevity in sedentary rats only resultsin an improvement in average survival, with no extension of maximallife span, when caused by exercise. In a previous study (J. O. Holloszyand K. B. Schechtman. J. Appl. Physiol. 70: 1529-1535, 1991), totest the possibility that exercise prevents the extension of life spanby food restriction, wheel running and food restriction were combined.The food-restricted runners showed the same increase in maximal lifespan as food-restricted sedentary rats but had an increased mortalityrate during the first one-half of their mortality curve. The purpose ofthe present study was to determine the pathological cause of thisincreased early mortality. However, in contrast to our previousresults, the food-restricted wheel-running rats in this study showed no increase in early mortality, and their survival curves were virtually identical to those of sedentary animals that were food restricted so asto keep their body weights the same as those of the runners. Thus it ispossible that the rats in the previous study had a health problem thathad no effect on longevity except when both food restriction andexercise were superimposed on it. Possibly of interest in this regard,the rats in this study did considerably more voluntary running thanthose in the previous study. It is concluded that1) moderate caloric restrictioncombined with exercise does not normally increase the early mortalityrate in male rats, 2) exercise doesnot interfere with the extension of maximal life span by foodrestriction, and 3) the beneficialeffects of food restriction and exercise on survival are not additiveor synergistic.

     

Exercise training restores decreased cellular immune functions in obese Zucker rats

Moriguchi, S., M. Kato, K. Sakai, S. Yamamoto, and E. Shimizu. Exercise training restores decreased cellular immune functions in obese Zucker rats. J. Appl.Physiol. 84(1): 311-317, 1998.This studyinvestigated whether exercise training had a beneficial effect on thedecreased mitogen response and improved a decreased expression ofglucose transporter 1 (GLUT-1) in splenocytes from obese Zucker rats.Experimental groups were lean and sedentary and exercise-trained obeseZucker rats. Exercise training, running on a motor-driven treadmill for5 days/wk for 40 wk, did not induce a significant decrease in bodyweight in obese Zucker rats. The plasma insulin concentration, showinga significant increase compared with lean Zucker rats, was unaffectedby exercise training. However, the plasma triglyceride concentration inobese Zucker rats was significantly depressed by exercise training,whereas it was still higher than that in lean Zucker rats. In addition,natural killer cell activity and concanavalin A-induced mitogenesis ofsplenic lymphocytes of obese Zucker rats were significantly restored. In these splenic lymphocytes, glucose uptake was significantly lowercompared with that in lean Zucker rats, which was also improved byexercise training. Although the expression of GLUT-1, the major glucosetransporter in immune cells, was depressed in splenic lymphocytes ofobese Zucker rats, exercise training induced a significant improvement.These results suggest that exercise training has a beneficial effect onthe decreased cellular immune functions in obese Zucker rats, which isassociated, in part, with the improvement in GLUT-1 expression.

     

Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase

Galliven, E. A., A. Singh, D. Michelson, S. Bina, P. W. Gold, and P. A. Deuster. Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase.J. Appl. Physiol. 83(6):1822-1831, 1997.Two studies, each utilizing short-term treadmillexercise of a different intensity, assessed the metabolic and hormonalresponses of women to exercise in the morning (AM) and late afternoon(PM). In study 1, plasmaconcentrations of growth hormone, arginine vasopressin, catecholamines,adrenocorticotropic hormone, cortisol, lactate, and glucose weremeasured before, during, and after high-intensity exercise (90%maximal O₂ uptake) in the AM andPM. In study 2, plasma concentrationsof adrenocorticotropic hormone, cortisol, lactate, andglucose were measured before, during, and aftermoderate-intensity exercise (70% maximalO₂ uptake) in the AM and PM in thefollicular (days 3-9), midcycle (days 10-16), and luteal(days 18-26) phases of themenstrual cycle. The results of studies1 and 2 revealed nosignificant diurnal differences in the magnitude of responses for anymeasured variable. In addition, study2 revealed a significant time-by-phase interaction forglucose (P = 0.014). However, netintegrated responses were similar across cycle phases. These datasuggest that metabolic and hormonal responses to short-term,high-intensity exercise can be assessed with equal reliability in theAM and PM and that there are subtle differences in blood glucoseresponses to moderate-intensity exercise across menstrual cycle phase.

     

Effects of training and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men

Crouse, Stephen F., Barbara C. O'Brien, Peter W. Grandjean,Robert C. Lowe, J. James Rohack, and John S. Green. Effects oftraining and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men. J. Appl.Physiol. 83(6): 2019-2028, 1997.To differentiatebetween transient (acute) and training (chronic) effects of exercise attwo different intensities on blood lipids and apolipoproteins (apo), 26 hypercholesterolemic men (cholesterol = 258 mg/dl, age = 47 yr, weight = 81.9 kg) trained three times per week for 24 wk, 350 kcal/session athigh (80% maximal O₂ uptake,n = 12) or moderate (50% maximalO₂ uptake, n = 14) intensity. Serum lipid andapolipoprotein (apo) concentrations (plasma volume adjusted) weremeasured before and immediately, 24, and 48 h after exercise on fourdifferent occasions corresponding to 0, 8, 16, and 24 wk of training.Data were analyzed using three-way repeated-measures multivariateanalysis of variance followed by analysis of variance and Duncan'sprocedures ( = 0.05). A transient 6% rise inlow-density-lipoprotein cholesterol measured before training at the24-h time point was no longer evident after training. Triglyceridesfell and total cholesterol, high-density-lipoprotein cholesterol(HDL-C), HDL₃-C, apo A-I, and apoB rose 24-48 h after exercise regardless of training or intensity.Total cholesterol, HDL₃-C, apoA-I, and apo B were lower andHDL₂-C was higher after trainingthan before training. Thus exercise training and a single session ofexercise exert distinct and interactive effects on lipids andapolipoproteins. These results support the practice of training atleast every other day to obtain optimal exercise benefits.

     

Effects of 4wk of hindlimb suspension on skeletal muscle mitochondrial respiration in rats

Yajid, Fatima, Jacques G. Mercier, Béatrice M. Mercier, Hervé Dubouchaud, and Christian Préfaut.Effects of 4 wk of hindlimb suspension on skeletal musclemitochondrial respiration in rats. J. Appl.Physiol. 84(2): 479-485, 1998.We investigated inrats the effect of 4 wk of hypodynamia on the respiration of mitochondria isolated from four distinct muscles [soleus,extensor digitorum longus, tibial anterior, and gastrocnemius(Gas)] and from subsarcolemmal (SS) and intermyofibrillar (IMF)regions of mixed hindlimb muscles that mainly contained the four citedmuscles. With pyruvate plus malate as respiratory substrate, 4 wk ofhindlimb suspension produced an 18% decrease in state3 respiration for IMF mitochondria compared with thosein the control group (P < 0.05). TheSS mitochondria state 3 were notsignificantly changed. Concerning the four single muscles, themitochondrial respiration was significantly decreased in the Gasmuscle, which showed a 59% decrease in state3 with pyruvate + malate(P < 0.05). The other musclespresented no significant decrease in respiratory rate in comparisonwith the control group. With succinate + rotenone, there was nosignificant difference in the respiratory rate compared with therespective control group, whatever the mitochondrial origin (SS, orIMF, or from single muscle). We conclude that 4 wk of hindlimbsuspension alters the respiration of IMF mitochondria in hindlimbskeletal muscles and seems to act negatively on complex I of theelectron-transport chain or prior sites. The muscle mitochondria mostaffected are those isolated from the Gas muscle.

     

Hypothyroidism alters diaphragm muscle development

Sieck, Gary C., Louise E. Wilson, Bruce D. Johnson, andWen-Zhi Zhan. Hypothyroidism alters diaphragm muscle development. J. Appl. Physiol. 81(5):1965-1972, 1996.The impact of hypothyroidism (Hyp) onmyosin heavy chain (MHC) isoform expression, maximum specific force(P_o), fatigability, and maximumunloaded shortening velocity(V_o) wasdetermined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with6-n-propyl-2-thiouracil (0.05% indrinking water) beginning at gestational day10 and was confirmed by reduced plasma levels of3,5,3-triiodothyronine and thyroxine. MHC isoforms wereseparated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. IsometricP_o and fatigue resistance of theDia were measured in vitro at 26°C, andV_o was determined at 15°C with the slack test. Compared with control muscles,expression of MHC-slow was higher and expression of adult fast MHCisoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day28. At each age,P_o and fatigability were reducedand V_o was slowerin the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.

     

Effect of resistance exercise training on cortical and cancellous bone in mature male rats

Westerlind, Kim C., James D. Fluckey, Scott E. Gordon,William J. Kraemer, Peter A. Farrell, and Russell T. Turner.Effect of resistance exercise training on cortical and cancellousbone in mature male rats. J. Appl.Physiol. 84(2): 459-464, 1998.The effect ofresistance training on tibial cancellous and cortical bone wasevaluated in rats by using static histomorphometry and Northernanalysis. Five-month-old male Sprague-Dawley rats were randomlyassigned to exercise (Ex; n = 8) orcontrol (Con; n = 4) groups. Animalswere operantly conditioned to press two levers, facilitating fullextension and flexion of the hindlimbs ("squats"), while wearingan unweighted vest. After an 8-wk familiarization period, Ex animalsperformed 3 sessions/wk for 17-19 sessions with progressivelyincreased amounts of weight applied to the vest. Con rats completed thesame exercise protocol without applied resistance. No difference incross-sectional, medullary, or cortical bone area was observed betweenEx and Con rats in the tibial diaphysis. In contrast, the cancellousbone area in the proximal tibial metaphysis was significantly larger intrained rats. Trabecular number, trabecular thickness, and thepercentage of cancellous bone covered by osteoid were significantlygreater in the Ex animals compared with Con animals. In addition,steady-state mRNA levels for osteocalcin for the Ex group were 456%those expressed in the Con group. The data demonstrate that resistancetraining increases cancellous bone area in sexually mature male ratsand suggest that it does so, in part, by stimulating bone formation.

     

A role for gastrointestinal endotoxins in enhancement of heat tolerance by physical fitness

Sakurada, Sotaro, and J. Robert S. Hales. A role forgastrointestinal endotoxins in enhancement of heat tolerance by physical fitness. J. Appl. Physiol.84(1): 207-214, 1998.To further elucidate mechanisms underlyingthe higher heat tolerance of physically fit compared with sedentarypeople, we have investigated the possibility that endotoxins (ofgastrointestinal origin) act, as in the normal development of fever, toraise body temperature and therefore reduce heat tolerance. In aninitial series of experiments, five physically fit and four sedentarysheep were exposed twice at rest to an environment of 42/35°C(dry/wet bulb temperature). When animals were given normal saline iv,rectal temperature (T_re) rose at a significantly higherrate in sedentary than in fit animals; this confirms that heattolerance is improved by physical fitness. Treatment withiv indomethacin did not affect the rate of rise of T_re infit animals. In sedentary animals, however, T_re was loweredto approximate that of fit animals. Because indomethacin blocksprostaglandin pathways involved in endotoxin-induced fever, theindomethacin-induced improvement of heat tolerance of sedentary but notfit animals supports the contention that endotoxins play a role indetermining that difference in heat tolerance. In a second series ofexperiments, quantitative cardiovascular measurements were made byusing radioactive microspheres. Under normothermic conditions, bloodflows in the brain, ileum, and diaphragm were higher in fit than insedentary animals. During hyperthermia up to T_re of42°C (in a 42/39°C environment), fit compared with sedentary animals exhibited 1) a greaterincrease in cardiac output, 2) anincrease in blood flow through arteriovenous anastomoses to higher andbetter maintained levels, 3) lessreduction in blood flow to the ileum, and4) greater increase in blood flowsto the myocardium, turbinates, nasal mucosa, and respiratorymuscles. Endotoxins are likely to come from the gut lumen,because reduction of gut blood flow forms part of the normal responseto heat stress. We suggest that improvement of heat tolerance byphysical fitness is caused by a greater cardiovascular capacity thatpermits not only greater perfusion of heat-loss tissues but themaintenance of a better gastrointestinal tract blood supply, therebybetter maintaining the normal barrier to movement of endotoxins from gut lumen to plasma. Sedentary people, with their lower cardiovascular capacity, redistribute more blood flow away from the gut during environmentally induced hyperthermia, thus allowing endotoxin-induced fever to aggravate hyperthermia.

     

Training intensity, blood lipids, and apolipoproteins in men with high cholesterol

Crouse, Stephen F., Barbara C. O'Brien, Peter W. Grandjean,Robert C. Lowe, J. James Rohack, John S. Green, and Homer Tolson. Training intensity, blood lipids, and apolipoproteins in men withhigh cholesterol. J. Appl. Physiol.82(1): 270-277, 1997.Twenty-six hypercholesterolemic men (meancholesterol, 258 mg/dl; age, 47 yr; weight, 81.9 kg) completed 24 wk ofcycle ergometer training (3 days/wk, 350 kcal/session) at either high(n = 12) or moderate (n = 14) intensity (80 and 50%maximal O₂ uptake, respectively, randomly assigned) to test the influence of training intensity on bloodlipid and apolipoprotein (apo) concentrations. Allphysiological, lipid, and apo measurements were completed at 0, 8, 16, and 24 wk. Lipid data were analyzed via two × fourrepeated-measures analysis of variance ( = 0.0031). Trainingproduced a significant decrease in body weight and increase in maximalO₂ uptake. No interactions betweenintensity and weeks of training were noted for any lipid or apovariable, and no between-group differences were significant before orthroughout training. Therefore, intensity did not affect the trainingresponse. Regardless of intensity, apo AI and apo B fell 9 and 13%,respectively, by week 16 and remainedlower through week 24 (P < 0.0003). Total cholesterol felltransiently (5.5%) by week 16 (P < 0.0021) but returned to initiallevels by week 24. Triglyceride,low-density-lipoprotein cholesterol, and high-density-lipoprotein (HDL)cholesterol did not change with training. In contrast,HDL₂ cholesterol rose 79% aboveinitial levels by week 8 and 82%above initial levels by week 24 (P < 0.0018);HDL₃ cholesterol fell 8 and 13%over the same training intervals (P < 0.0026). These data show that changes in blood lipid and apoconcentrations that accompany training in hypercholesterolemic men arenot influenced by exercise intensity when caloric expenditure is heldconstant.

     

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women

Brooks, E. M., A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O'Gorman, J. A. Derr, and W. L. Kenney. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J. Appl.Physiol. 83(2): 477-484, 1997.This investigationexamined effects of chronic (2 yr) hormone replacement therapy (HRT),both estrogen replacement therapy (ERT) and estrogen plus progesteronetherapy (E+P), on core temperature and skin blood flow responses ofpostmenopausal women. Twenty-five postmenopausal women [9 not onHRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for1 h at an ambient temperature of 36°C. Cutaneous vascularconductance (CVC) was monitored by laser-Doppler flowmetry, and forearmvascular conductance (FVC) was measured by using venous occlusionplethysmography. Iontophoresis of bretylium tosylate was performedbefore exercise to block local vasoconstrictor (VC) activity at oneskin site on the forearm. Rectal temperature (T_re) was ~0.5°C lower forthe ERT group (P < 0.01) comparedwith E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (T_b) and CVC:T_b curves were shifted~0.5°C leftward for the ERT group(P < 0.0001). Baseline CVC wassignificantly higher in the ERT group(P < 0.05), but there was nointeraction between bretylium treatment and groups once exercise wasinitiated. These results suggest that1) chronic ERT likely acts centrally to decrease T_re,2) ERT lowers theT_re at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition ofexogenous progestins in HRT effectively blocks these effects.

     

In vivo assessment of changes in air and tissue volumes after pneumonectomy

Takeda, S., E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia. In vivo assessment of changes in air and tissue volumes after pneumonectomy. J. Appl.Physiol. 82(4): 1340-1348, 1997.We examined theprogression and topographical distribution of postpneumonectomy volumechanges in immature foxhounds undergoing right pneumonectomy (R-Pnx,n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequentlyraised to maturity. Volumes of lung air (Vair) and tissue(Vti) were estimated by computerized tomography (CT) scan at 7, 22, and52 wk after surgery at a transpulmonary pressure of 20 cmH₂O. Estimates of Vti by CT scanincluded both septal tissue as well as nonseptal tissue (small- andmedium-sized airways and blood vessels); these were compared withestimates of septal Vti by an acetylene rebreathing (Rb) method. Wefound significant correlations between these techniques(Vair_CT = 0.83 Vair_Rb + 275, R = 0.97;Vti_CT = 1.62 Vti_Rb  30, R = 0.81). Extravascular septal Vtireturned to normal 7 wk after R-Pnx and remained normal up to maturity.Nonseptal Vti remained significantly below normal. The greatestincrease in Vti occurred in the midlung region just cephalad and caudalto the heart. After an early period of accelerated tissue growth afterR-Pnx, the rate of septal tissue growth matched that of somatic growth,whereas nonseptal tissue growth lagged behind. Compensatory growth ofthe remaining left lung was not associated with selectivealterations in thoracic development.

     

Influence of pregnancy on the febrile response to ICV administration of PGE1 in rats studied in a thermocline

Eliason, Heather L., and James E. Fewell. Influence ofpregnancy on the febrile response to ICV administration ofPGE₁ in rats studied in athermocline. J. Appl. Physiol. 82(5):1453-1458, 1997.Rats near term of pregnancy have an attenuatedfebrile response to intracerebroventricular (ICV) injection ofprostaglandin E₁ (PGE₁) when they are studied atan ambient temperature below their thermoneutral zone. Given thatnonshivering thermogenesis in brown adipose tissue is impaired inrodents near term of pregnancy, it is possible that the attenuatedfebrile response is forced by impairment of this component of theautonomic thermoregulatory response. If this were the case, thennear-term pregnant rats should develop a "normal" fever afterPGE₁ administration if they werestudied in a thermocline where they could utilize behavioral as well asautonomic thermoregulatory effectors to increase their body coretemperature (T_bc). Experimentswere, therefore, carried out on 13 nonpregnant and 14 pregnantchronically instrumented rats in a thermocline (temperature gradient10-40°C) to investigate theirT_bc responses to ICV injection ofPGE₁. ICV injection of 0.2 µgPGE₁ produced significantincreases in T_bc and fever index in both nonpregnant and pregnant animals (day19 of gestation); the increases, however, weresignificantly attenuated in the pregnant compared with the nonpregnantrats. Behavioral (e.g., selected ambient temperature) and autonomic(e.g., oxygen consumption) thermoregulatory effectors were activated toincrease T_bc after ICVPGE₁ in both groups of animals,but the duration of activation was shortened in pregnant compared withnonpregnant rats. The abbreviated thermoregulatory effector responsesand the resulting attenuated febrile response toPGE₁ in the pregnant rats may have resulted from a pregnancy-related activation of an endogenous antipyretic system.