Age-dependent core temperature responses of conscious rabbits to acute hypoxemia.

Experiments were carried out on chronically instrumented newborn and older rabbits to characterize their core temperature (T(c)) responses to acute hypoxemia and to differentiate "forced" vs. "regulated" thermoregulatory responses. Three age ranges of kits were studied: 4-6, 9-11, and 28-30 days of age. During an experiment, T(c), selected ambient temperature (T(a)), and oxygen consumption were measured from kits studied in a thermocline during a control period of normoxemia, an experimental period of normoxemia or hypoxemia (fraction of inspired oxygen 0.10), and a recovery period of normoxemia. We reasoned that no change or a decrease in T(a) while T(c) decreased during hypoxemia would indicate a regulated thermoregulatory response, whereas an increase in T(a) while T(c) decreased during hypoxemia would indicate a forced thermoregulatory response. T(c) decreased during acute hypoxemia in the older kits but not in the 4- to 6-day-old kits; the decrease in T(c) was accentuated on postnatal days 28-30 compared with postnatal days 9-11. T(a) decreased or stayed the same during exposure to acute hypoxemia. Our data provide evidence that postnatal maturation influences the T(c) response of rabbits to acute hypoxemia and that the decrease in T(c) during hypoxemia in the older kits results from a regulated thermoregulatory response.     

Autonomic and behavioral thermoregulation in guinea pigs during postnatal maturation

Fewell, James E., Maria Kang, and Heather L. Eliason.Autonomic and behavioral thermoregulation in guinea pigs during postnatal maturation. J. Appl.Physiol. 83(3): 830-836, 1997.Serial experimentswere carried out on seven chronically instrumented Hartley-strainguinea pigs at 1, 3, and 5 wk of age to define their autonomic andbehavioral thermoregulatory profiles and to test the hypothesis thatthey have the mechanisms in place shortly after birth that allow themto optimize their energy expenditure for thermoregulation by selectinga thermal environment that requires the lowest metabolic oxygenrequirements. Each animal was studied in both a thermocline todetermine selected ambient temperature and in a metabolic chamberto determine the thermoregulatory response to forced changes in ambienttemperature. In the thermocline, the guinea pigs at all postnatal agesselected an ambient temperature that placed core temperature, oxygenconsumption, thermal conductance, heart rate, and respiratory rate atlevels comparable to those observed at ambient temperatures in whichminimal oxygen consumption occurred in the metabolic chamber. Thus ourexperiments provide evidence that guinea pigs have theneurophysiological mechanisms in place shortly after birth that allowthem to optimize their energy expenditure for thermoregulation byselecting a thermal environment that corresponds to the lowestmetabolic oxygen requirements.

     

Relationship between T-wave amplitude and oxygen pulse in guinea pigs in hyperbaric helium and hydrogen

Diving isknown to induce a change in the amplitude of the T wave(A_Tw) ofelectrocardiograms, but it is unknown whether this is linked to achange in cardiovascular performance. We analyzed A_Tw in guinea pigs at 10-60atm and 25-36°C, breathing 2%O₂ in either helium (heliox;n = 10) or hydrogen (hydrox;n = 9) for 1 h at each pressure. Coretemperature and electrocardiograms were detected by using implantedradiotelemeters. O₂ consumption rate was measured by using gas chromatography. In a previous study (S. R. Kayar and E. C. Parker. J. Appl.Physiol. 82: 988-997, 1997), we analyzed theO₂ pulse, i.e., theO₂ consumption rate per heartbeat, in the same animals. By multivariate regression analysis, weidentified variables that were significant toO₂ pulse: body surface area,chamber temperature, core temperature, and pressure. In this study,inclusion of A_Tw made asignificantly better model with fewer variables. After normalizing forchamber temperature and pressure, theO₂ pulse increased with increasing A_Tw in heliox(P = 0.001) but with decreasingA_Tw in hydrox(P < 0.001). ThusA_Tw is associated with thedifferences in O₂ pulse foranimals breathing heliox vs. hydrox.

     

Naloxone reduces decrease in ventilation induced by hypoxia in newborn infants

The mechanism responsible for the decrease in ventilation during breathing of low fractional concentration of inspired O2 in the newborn infant is poorly understood. The present study tested the hypothesis that endogenous opiates account for this ventilatory decrease. Eleven healthy newborn infants breathed 15% O2, balance N2 for 5 min following an injection of saline and following an injection of naloxone. Neither injection caused a change in minute ventilation (VE) or ventilatory pattern when the infants were breathing room air. However, the decreased ventilation during hypoxia following naloxone was significantly less than that following saline. VE dropped about 14% following saline but only about 4% following naloxone. However, the adult ventilatory response to hypoxemia, i.e., a relatively sustained increase in VE, was not attained. Naloxone had no influence on the occurrence of periodic breathing during hypoxemia. Thus in the healthy full-term newborn infant, endogenous opiates account only for a part of the decreased ventilation during hypoxemia.     

Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs

Bonham, A. C., K. S. Kott, and J. P. Joad. Sidestreamsmoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs. J. Appl.Physiol. 81(4): 1715-1722, 1996.We determinedthe effect of sidestream tobacco smoke (SS) exposure on responses oflung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr),and arterial blood pressure (ABP) to substance P in young guinea pigs.Guinea pigs were exposed to SS or filtered air fromday 8 to days41-45 of life. They were then anesthetized andgiven three doses of intravenous substance P (1.56-4.94 nmol/kg).SS exposure augmented substance P-evoked increases in RAR activity(P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP.Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuatedsubstance P-evoked increases in RAR activity(P = 0.001) and ABP(P = 0.009) but not in peak Ptr(P = 0.06). Thus chronic exposure toSS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airwayhyperresponsiveness and cough in children chronically exposed toenvironmental tobacco smoke.

     

Effect of hypoxia on respiratory system impedance in dogs

Simon, B. A., P. B. Zanaboni, and D. P. Nyhan. Effectof hypoxia on respiratory system impedance in dogs. J. Appl. Physiol. 83(2): 451-458, 1997.The effects of hypoxia on lung and airwaymechanics remain controversial, possibly because of the confoundingeffects of competing reflexes caused by systemic hypoxemia. We comparedthe effects of systemic hypoxemia with those of unilateral alveolarhypoxia (with systemic normoxemia) on unilateral respiratory systemimpedance (Z) in intact, anesthetized dogs. Independent lungventilation was obtained with a Kottmeier endobronchial tube.Individual left and right respiratory system Z was measured duringsinusoidal forcing with 45 ml of volume at frequencies of 0.2-2.1Hz during control [100% inspiredO₂ fraction(FI_O2)], systemichypoxemia (10% FI_O2), andunilateral alveolar hypoxia (0%FI_O2 to left lung, 100%FI_O2 to right lung). Duringsystemic hypoxemia, there was a mean Z magnitude increase of 18%. Thischange was entirely attributable to a decrease in the imaginarycomponent of Z; there was no change in the real component of Z. Administration of atropine (0.2 mg/kg) did not block the increase in Zwith systemic hypoxemia. In contrast, there was no change in Z in thelung subjected to unilateral alveolar hypoxia. We conclude thatalveolar hypoxia has no direct effect on lung mechanical properties inintact dogs. In contrast, systemic hypoxemia does increase lungimpedance, apparently through a noncholinergic mechanism.

     

Catecholamine concentrations in plasma and organs of the fetal guinea pig during normoxemia, hypoxemia, and asphyxia

To examine the responses of the sympatho-adrenal system to reduced oxygen supply we studied plasma and tissue concentrations of catecholamines during normoxemia, hypoxemia, and asphyxia in 22 fetal guinea pigs near term. Fetal blood was obtained by cardiopuncture in utero under ketamine/xylazine-anesthesia. Catecholamines were determined in plasma and tissue of 15 organs and 14 brain parts by HPLC-ECD. During normoxemia (SO2 54 +/- 4 (SE) %, pH 7.36 +/- 0.02, n = 5) plasma catecholamine levels were low (norepinephrine 447 +/- 53, epinephrine 42 +/- 12, dopamine 44 +/- 6 pg/ml). During hypoxemia (SO2 27 +/- 3%, pH 7.32 +/- 0.01, n = 6) and asphyxia (SO2 24 +/- 2%, pH 7.23 +/- 0.02, n = 11) tissue catecholamine concentrations changed with changing blood gases and with increasing plasma catecholamines. Norepinephrine concentrations increased in both skin and lung and decreased in liver, pancreas, and scalp; those of epinephrine increased in the heart, lung liver, and scalp and decreased in the adrenal. There were only minor changes in brain catecholamine concentrations except for a 50% reduction in dopamine in the caudate nucleus. Concentrations of dopamine catabolite 3,4-dihydroxyphenylacetic acid decreased in many brain parts, suggesting that cerebral catecholamine metabolism was affected by hypoxemia and asphyxia. We conclude that the sympatho-adrenal system of fetal guinea pigs near term is mature and that its stimulation by reduced fetal oxygen supply leads to changes in both plasma and tissue catecholamine concentrations.     

Effect of urokinase on disseminated intravascular coagulation

Our studyevaluated the possible therapeutic effect of urokinase in treating themicrothrombiotic effects of disseminated intravascular coagulation byassisting the activation of endogenous plasminogen. Twenty-six pigswere anesthetized, intubated, mechanically ventilated, and surgicallycatheterized. Septic shock was induced in all 26 pigs by an intravenousinfusion of heat-killed Escherichia coli. The pigs were divided into two sets ofexperiments: in experiment 2 (n = 14), one-half received anintravenous dose of urokinase 1 h after heat-killed E. coli infusion and in experiment3 (n = 12) one-halfreceived an intravenous bolus dose and a continuous drip of urokinase 2 h after heat-killed E. coli infusion.The untreated pigs served as controls. Hemodynamic parameters, blood chemistries, and blood gases were analyzed. Urokinase given 1 h afterbacterial toxin infusion significantly restored blood flow, resultingin an increase in cardiovascular and pulmonary function and improvedsurvival rate (43% control vs. 100% treated, 24-h experimentalperiod). Treatment given after 2 h showed some significant effect onpulmonary function; however, within 10 h of E. coli infusion, mortality rates in control and treatedgroups were 100 and 83%, respectively. Early administration ofurokinase after onset of disseminated intravascular coagulationrestored blood flow and helped resolve organ damage.

     

"Living high-training low": effect of moderate-altitude acclimatization with low-altitude training on performance

Levine, Benjamin D., and James Stray-Gundersen."Living high-training low": effect of moderate-altitudeacclimatization with low-altitude training on performance.J. Appl. Physiol. 83(1): 102-112, 1997.The principal objective of this study was to test the hypothesisthat acclimatization to moderate altitude (2,500 m) plus training atlow altitude (1,250 m), "living high-training low," improvessea-level performance in well-trained runners more than an equivalentsea-level or altitude control. Thirty-nine competitive runners (27 men,12 women) completed 1) a 2-wklead-in phase, followed by 2) 4 wkof supervised training at sea level; and3) 4 wk of field training camprandomized to three groups: "high-low"(n = 13), living at moderate altitude(2,500 m) and training at low altitude (1,250 m); "high-high"(n = 13), living and training atmoderate altitude (2,500 m); or "low-low"(n = 13), living and training in amountain environment at sea level (150 m). A 5,000-m time trial was theprimary measure of performance; laboratory outcomes included maximalO₂ uptake(O_{2 max}), anaerobic capacity (accumulated O₂ deficit),maximal steady state (MSS; ventilatory threshold), running economy,velocity at O_{2 max}, and blood compartment volumes. Both altitude groups significantly increased O_{2 max}(5%) in direct proportion to an increase in red cell mass volume(9%; r = 0.37, P < 0.05), neither of which changedin the control. Five-kilometer time was improved by the field trainingcamp only in the high-low group (13.4 ± 10 s), in directproportion to the increase inO_{2 max}(r = 0.65, P < 0.01). Velocity atO_{2 max} andMSS also improved only in the high-low group. Four weeks of livinghigh-training low improves sea-level running performance in trainedrunners due to altitude acclimatization (increase in red cell massvolume and O_{2 max}) and maintenance of sea-level training velocities, mostlikely accounting for the increase in velocity atO_{2 max} and MSS.

     

PKC regulation of cardiac CFTR Cl- channel function in guinea pig ventricular myocytes

The role ofprotein kinase C (PKC) in regulating the protein kinase A(PKA)-activated Cl currentconducted by the cardiac isoform of the cystic fibrosis transmembraneconductance regulator (cCFTR) was studied in guinea pig ventricularmyocytes using the whole cell patch-clamp technique. Althoughstimulation of endogenous PKC with phorbol 12,13-dibutyrate (PDBu)alone did not activate thisCl current, even whenintracellular dialysis was limited with the perforated patch-clamptechnique, activation of PKC did elicit a significant response in thepresence of PKA-dependent activation of the current by the-adrenergic receptor agonist isoproterenol. PDBuincreased the magnitude of theCl conductance activated bya supramaximally stimulating concentration of isoproterenol by 21 ± 3.3% (n = 9) when added afterisoproterenol and by 36 ± 16% (n = 14) when introduced before isoproterenol. 4-Phorbol12,13-didecanoate, a phorbol ester that does not activate PKC, did notmimic these effects. Preexposure to chelerythrine orbisindolylmaleimide, two highly selective inhibitors of PKC, significantly reduced the magnitude of the isoproterenol-activated Cl current by 79 ± 7.7% (n = 11) and 52 ± 10%(n = 8), respectively. Ourresults suggest that although acute activation of endogenous PKC alonedoes not significantly regulate cCFTRCl channel activity innative myocytes, it does potentiate PKA-dependent responses, perhapsmost dramatically demonstrated by basal PKC activity, which may play apivotal role in modulating the function of these channels.

     

Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres

Buchwalder, Lynn F., Michelle Lin, Thomas J. McDonald, andPeter W. Nathanielsz. Fetal sheep adrenal blood flow responses tohypoxemia after splanchnicotomy using fluorescent microspheres. J. Appl. Physiol. 84(1): 82-89, 1998.Adrenal gland blood flow (ABF) increases during hypoxemia infetal sheep, but regulation of ABF is poorly understood. The purpose ofthis study was to determine the effects of splanchnic nerve section onfetal ABF responses to hypoxemia using the fluorescent microsphere (FM) technique. At 125 days of gestation, 14 unanesthetized fetal sheep [bilateral splanchnicotomy (Splx,n = 6) and control (Cont,n = 8)] were injectedwith FM before and at 60 min ofN₂-induced hypoxemia (~40%decrease in fetal arterial PO₂).Adrenal tissue and reference blood samples were digested and filtered, and FM dye was extracted for spectrometer analysis. Baseline whole, medullary, and cortical ABF for the Cont group were similar to published values using radioactive microspheres and did not differ fromSplx values. Hypoxemia increased whole, medullary, and cortical ABF(mean ± SE) from baseline for the Cont group by 281 ± 35, 258 ± 31, and 496 ± 81% (P < 0.05). The increase for the Splx group was attenuated compared with theCont group (P < 0.05) for whole andmedullary ABF (139 ± 27 and 43 ± 27%) but not cortical ABF(326 ± 91%). We conclude that1) the FM technique is valid formeasuring fetal ABF and 2) in fetalsheep the splanchnic nerve is not necessary to maintain basal ABF butplays an important role in regulating the hypoxemia-induced increase inABF through the medullary, but not cortical, ABF response.

     

Level of ventilation influences the cardiovascular response to hypoxemia in lambs

Newborn animals of a number of species display a brisk increase in ventilation followed by a gradual drop toward or below baseline within minutes of exposure to acute hypoxemia. Heart rate and cardiac output (a determinant of systemic oxygen transport along with the arterial oxygen content) appear to follow a similar pattern, but whether or not the cardiovascular response is influenced by the respiratory response is unknown. We therefore carried out experiments in which the level of ventilation was controlled during normoxemia and hypoxemia to test the hypothesis that the level of ventilation influences the cardiovascular response to acute hypoxemia. Six lambs ranging in age from 17 to 22 days were anesthetized, tracheostomized, and instrumented for measurement of cardiovascular variables. A recovery period of at least 3 days was allowed before the study when each lamb was artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen in nitrogen. A control respiratory frequency (f) of 30 breaths per min was set and a control tidal volume (VT) was chosen to achieve normocapnia. Cardiovascular measurements were made during normoxemia and hypoxemia (FIO2 0.10) 5 min after f or VT was changed to simulate a decrease, no change, or an increase in ventilation. During normoxemia, the level of ventilation had little effect on the measured cardiovascular variables. At control levels of ventilation, hypoxemia caused an increase in cardiac output that was due solely to an increase in stroke volume as heart rate decreased; blood pressure was unchanged. Increasing ventilation during hypoxemia did not augment cardiac output or alter blood pressure as compared with that observed at control levels of ventilation. Decreasing ventilation during hypoxemia, however, decreased cardiac output due to a profound bradycardia; blood pressure increased significantly. Our data provide evidence that the level of ventilation significantly influences the cardiovascular response to hypoxemia in young lambs.     

Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction

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

     

Physical exercise and normobaric hypoxia: independent modulators of peripheral cholecystokinin metabolism in man

The purpose ofthe present investigation was to determine the independent effects ofhypoxia and physical exercise on peripheral cholecystokinin (CCK)metabolism in humans. Thirty-two physically active men wererandomly assigned in a double-blind manner to either a normoxic (N;n = 14) or hypoxic (H; n = 18) group.During the acute study, subjects in the H group only participated in two tests, separated by 48 h, which involved a cycling test to exhaustion in normobaric normoxia and normobaric hypoxia (inspired O₂ fraction = 0.21 and 0.16, respectively). In theintermittent study, N and H groups cycle-trained for 4 wk at the samerelative exercise intensity in both normoxia and hypoxia. Acutenormoxic exercise consistently raised plasma CCK during both studies by 290-723%, which correlated with increases in the plasma ratio offree tryptophan to branched chain amino acids (r = 0.58-0.71, P < 0.05). In contrast, acute hypoxicexercise decreased CCK by 7.0 ± 5.5 pmol/l, which correlated withthe decrease in arterial oxygen saturation (r = 0.56, P < 0.05). In the intermittent study, plasma CCKresponse at rest and after normoxic exercise was not altered afterphysical training, despite a slight decrease in adiposity. We concludethat peripheral CCK metabolism 1) is more sensitive to acutechanges than chronic changes in energy expenditure and 2) ispotentially associated with acute changes in tissue PO₂ and metabolic precursors of cerebralserotoninergic activity.

     

Effects of pregnancy and chronic hypoxia on contractile responsiveness to alpha 1-adrenergic stimulation

Decreasedcontractile response to vasoconstrictors in uterine and nonuterinevessels contributes to increased blood flow to the uterine circulationduring normal pregnancy. Pregnancies complicated by preeclampsiaand/or chronic hypoxia show a reversal or diminution of thesepregnancy-associated changes. We sought to determine whether chronichypoxia opposes the reduction in contractile response in uterine andnonuterine vessels during normal pregnancy and, if so, whetherdecreased basal nitric oxide (NO) activity was involved. We examinedthe contractile response to phenylephrine (PE) in guinea pig uterineartery (UA), mesenteric artery (MA), and thoracic aorta (TA) ringsisolated from nonpregnant or pregnant guinea pigs that had been exposedthroughout gestation to either low (1,600 m,n = 47) or high (3,962 m,n = 43) altitude. In the UA, pregnancyreduced contractile sensitivity to PE and did so similarly at low andhigh altitude (EC₅₀: 4.0 × 10⁸ nonpregnant, 9.3 × 10⁸ pregnant at lowaltitude; 4.8 × 10⁸nonpregnant, 1.0 ×10⁸pregnant at high altitude; both P < 0.05). Addition of the NO synthase inhibitornitro-L-arginine (NLA; 200 mM)to the vessel bath increased contractile sensitivity in the pregnant UA(P < 0.05) and eliminated the effectof pregnancy at both altitutes. NLA also raised contractile sensitivityin the nonpregnant high-altitude UA, but contractile response withoutNLA did not differ in the high- and low-altitude animals. In the MA,pregnancy decreased contractile sensitivity to PE at high altitudeonly, and this shift was reversed by NO inhibition. In the TA, neitherpregnancy nor altitude affected contractile response, but NO inhibition raised contractile response in nonpregnant and pregnant TA at bothaltitudes. We concluded that pregnancy diminished contractile responseto PE in the UA, likely as a result of increased NO activity, and thatthese changes were similar at low and high altitude. Counter to ourhypothesis, chronic hypoxia did not diminish the pregnancy-associatedreduction in contractile sensitivity to PE or inhibit basal NO activityin the UA; rather it enhanced, not diminished, basal NO activity in thenonpregnant UA and the pregnant MA.

     

Differential relaxant responses of pulmonary arteries and veins in lung explants of guinea pigs

Shi, Weibin, David H. Eidelman, and René P. Michel.Differential relaxant responses of pulmonary arteries and veins inlung explants of guinea pigs. J. Appl.Physiol. 83(5): 1476-1481, 1997.The endotheliumregulates vascular tone through release of relaxing or contractingfactors, with nitric oxide (NO) being a major endothelium-derivedrelaxing factor. In the present study, we used a lung explant techniqueto determine the differential abilities and mechanisms of pulmonaryarteries and veins of normal guinea pigs to relax after precontraction.Excised lungs of 15 guinea pigs were filled through the airways with1% agarose, cut into 1-mm-thick slices, and cultured overnight.Luminal areas of vascular cross sections were measured with animage-analysis system. Vessels were precontracted with U-46619, andresponses to histamine, acetylcholine (ACh), sodium nitroprusside, andpapaverine were examined. We also determined the effects ofN-nitro-L-arginineand of indomethacin on ACh-induced responses. We found that histaminerelaxed arteries more than veins and that ACh relaxed only arteries.N-nitro-L-arginine pretreatmentabolished ACh-induced relaxation of arteries and caused ACh-inducedcontraction of veins, whereas indomethacin markedly augmentedACh-induced relaxation of arteries (maximal relaxation: 48.5 ± 4.7 vs. 19.2 ± 5.1% without it) and induced a dose-dependentrelaxation of veins (maximal relaxation: 17.0 ± 4.1%). Sodiumnitroprusside induced a significantly greater relaxation of arteriesthan veins, whereas papaverine relaxed them equally. We conclude thatin guinea pigs endothelial NO-mediated relaxation is greater inpulmonary arteries than in veins and that ACh-induced NO-mediatedrelaxation is reduced by the simultaneous production ofcyclooxygenase-derived vasoconstrictors.

     

Is there evidence for an age-related reduction in metabolic rate?

To determinewhether the age-related reduction in basal metabolic rate (BMR) isexplained by a quantitative and/or qualitative change in thecomponents of lean tissue, we conducted a cross-sectional study ingroups of young (n = 38, 18-35yr) and older (n = 24, 50-77 yr)healthy individuals. BMR was measured by indirect calorimetry. Bodycomposition was obtained by using dual-energy X-ray absorptiometry (DEXA), which permitted four compartments to be quantified [bone mineral mass, fat mass (FM), appendicular lean tissue mass(A_LTM), and nonappendicular leantissue mass (NA_LTM)].Absolute BMR and A_LTM were lower,whereas FM was significantly higher in the older, compared with young,subjects. BMR, adjusted for differences in FM,A_LTM, andNA_LTM, was significantly lower inthe older subjects by 644 kJ/day. In separate regression analyses ofBMR on body compartments, older subjects had significantly lowerregression coefficients for A_LTMand NA_LTM, compared with youngsubjects. Hence, the age-related decline in BMR is partly explained bya reduction in the quantity, as well as the metabolic activity, ofDEXA-derived lean tissue components.

     

Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs

Matsumoto, Koichiro, Hisamichi Aizawa, Shohei Takata,Hiromasa Inoue, Naotsugu Takahashi, and Nobuyuki Hara.Nitric oxide derived from sympathetic nerves regulates airwayresponsiveness to histamine in guinea pigs. J. Appl.Physiol. 83(5): 1432-1437, 1997.Nitric oxide(NO), which can be derived from the nervous system or the epithelium ofthe airway, may modulate airway responsiveness. We investigated how NOderived from the airway nervous system would affect the airwayresponsiveness to histamine and acetylcholine in mechanicallyventilated guinea pigs. An NO synthase inhibitor N^G-nitro-L-argininemethyl ester (L-NAME) (1 mmol/kgip) significantly enhanced airway responsiveness to histamine but notto acetylcholine. Its enantiomerD-NAME (1 mmol/kg ip), incontrast, had no effect. TheL-NAME-induced airwayhyperresponsiveness was still observed in animals pretreated withpropranolol (1 mg/kg iv) and atropine (1 mg/kg iv). Pretreatment withthe ganglionic blocker hexamethonium (2 mg/kg iv) completely abolishedenhancing effect of L-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter theL-NAME-induced airwayhyperresponsiveness, whereas sympathetic stellatectomy completelyabolished it. Results suggest that NO that was presumably derived fromthe sympathetic nervous system regulates airway responsiveness tohistamine in guinea pigs.

     

Plasticity in Skeletal, Cardiac, and Smooth Muscle: Selected Contribution: IGF-I antibody prevents increases in protein synthesis in epitrochlearis muscles from refed, diabetic rats

The purpose of this study was to examine whether immune neutralizationof muscle-produced insulin-like growth factor I (IGF-I) would preventan appropriate anabolic response to refeeding in diabetic rats. MaleSprague-Dawley rats were made diabetic by partial pancreatectomy andwere randomly assigned to be either control-fed, fasted, orfasted-refed (n = 7-8 per group). Diabetes decreased rates of protein synthesis and increased rates of protein degradation in incubated epitrochlearis muscles (P < 0.05). In both groups of rats, fasting lowered protein synthesis andincreased proteolysis and subsequent refeeding returned both parameters to near basal values (P < 0.05). Neutralization ofmuscle IGF-I by the addition of IGF-I antibody to the incubation mediumreduced protein synthesis an average of 22% for all groups(P < 0.05). However, rates of protein degradation werenot affected. In nondiabetic rats, refeeding increased proteinsynthesis in both control and antibody-treated muscles(P < 0.05). Refeeding also increased protein synthesisin the control muscles from diabetic rats (P < 0.01).In contrast, muscles from diabetic rats that were incubated withanti-IGF-I did not increase protein synthesis in response to refeeding.These data suggest that immune neutralization of muscle IGF-I inhypoinsulinemic rats negated the ability of endogenous IGF-I to promoteprotein synthesis and thereby prevented an appropriate anabolic response.

     

Behavioral Thermoregulation and the "Final Preferendum" Paradigm

Wider attention to Fry's (1947) "final preferendum" paradigmwould facilitate comparative studies of temperature preference(behavioral thermoregulation) among different animal groups.According to Fry's bipartite definition, the final preferendumis that temperature at which preference and acclimation areequal, and to which an animal in a thermal gradient will finallygravitate regardless of its prior thermal experience (acclimation).This paradigm is helpful in distinguishing between acute thermalpreferenda (measured within 2 hr or less after placing an animalin a thermal gradient), which are influenced by acclimationtemperature, and the species-specific final preferendum (measured24–96 hr after placement in the gradient), which is essentiallyindependent of prior acclimation because reacclimation occursduring the gravitation process. The paradigm does not take intoaccount non-thermal acclimatization influences (e.g., season,photoperiod, age, light intensity, salinity, disease, nutrition,pollutants, biotic interactions) which can also affect temperaturepreference. However, a graph of acutely preferred temperaturesversus acclimation temperatures can be employed to determinean equivalent acclimation temperature for any given acclimatizationstate, as a simple means of quantifying acclimatization statesresulting from interactions of many influences. This paradigm,developed for use with fishes, can also be applied to otherectothermic taxa, although it is most easily employed with aquaticorganisms because of the simplicity of specifying aquatic thermalenvironments in terms of water temperature alone. Methodologiesused in studies of behavioral thermoregulation should take theparadigm into account (especially with respect to length oftests) to enhance the comparative value of data across taxa.