Thermoregulatory control during pregnancy and lactation in rats

Eliason, Heather L., and James E. Fewell.Thermoregulatory control during pregnancy and lactation in rats.J. Appl. Physiol. 83(3): 837-844, 1997.Although the mechanisms remain unknown, maternal coretemperature (T_c) decreases nearterm of pregnancy and is increased throughout lactation in rats. Thepurpose of our present experiments was to determine whether pregnancy and lactation shift the thermoneutral zone of rats and to investigate whether the changes in maternal T_cduring pregnancy and lactation result from "forced" or"regulated" thermoregulatory responses. Conscious, chronicallyinstrumented nonpregnant and pregnant and lactating rats were studiedboth in a thermocline (a chamber with a linear temperature gradientfrom 12 to 36°C) and in a metabolic chamber to determine theinfluence of pregnancy and lactation on selected ambient temperature aswell as the thermoregulatory response to changes in ambienttemperature. We found that selected ambient temperature, oxygenconsumption, and thermal conductance did not change in rats studied ina thermocline as T_c decreased nearterm of pregnancy. There was, however, a downward shift in thethermoneutral zone of rats studied in a metabolic chamber near term ofpregnancy. During lactation, selected ambient temperature decreased inrats studied in a thermocline as oxygen consumption andT_c increased. The thermoneutralzone of lactating rats was not different from that of nonpregnantanimals. Thus our data provide evidence that the decrease inT_c near term of pregnancy in ratsresults from a regulated thermoregulatory response,whereas the increase in T_c duringlactation results from a forced thermoregulatory response.

     

Pregnancy alters body-core temperature response to a simulated open field in rats

Fewell, James E., and Patricia A. Tang. Pregnancyalters body-core temperature response to a simulated open field in rats. J. Appl. Physiol. 82(4):1406-1410, 1997.Exposure of a rat to a novel environment (e.g.,a simulated open field) induces a transient increase in body-coretemperature, which is often called stress-induced hyperthermia.Although pregnancy is known to influence thermoregulatory control, itseffect on stress-induced hyperthermia is unknown. Therefore, 24 Sprague-Dawley rats (8 nonpregnant and 16 pregnant) were studied totest the hypothesis that pregnancy would alter the development ofstress-induced hyperthermia after exposure to a simulated open field.Body-core temperature index increased significantly after exposure to asimulated open field in nonpregnant and gestationday-10 rats but not in gestation day-15 andday-20 rats. Thus our data provideevidence that pregnancy influences the body-core temperature responseof rats exposed to a simulated open field in a gestation-dependentfashion. The functional consequences as well as the mechanisms involvedremain to be determined.

     

A relationship between heat loss and sleepiness: effects of postural change and melatonin administration

Kräuchi, Kurt, Christian Cajochen, and AnnaWirz-Justice. A relationship between heat loss and sleepiness:effects of postural change and melatonin administration.J. Appl. Physiol. 83(1): 134-139, 1997.Both the pineal hormone melatonin (Mel) and postural changeshave thermoregulatory sequelae. The purpose of the study was toevaluate their relationship to subjective sleepiness. Eight healthyyoung men were investigated under the unmasking conditions of aconstant routine protocol. Heart rate, rectal temperature(T_re), skin temperatures (foot,T_fo; and stomach), and subjectivesleepiness ratings were continuously recorded from 1000 to 1700. Mel (5 mg po) was administered at 1300, a time when Mel should not phaseshift the circadian system. Both the postural change at1000 from upright to a supine position (lying down in bed) and Meladministration at 1300 reduced T_reand increased T_fo in parallel withincreased sleepiness. These findings suggest that under comfortableambient temperature conditions, heat loss via the distal skin regions(e.g., feet) is a key mechanism for induction of sleepiness as corebody temperature declines.

     

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.

     

Influence of nicotine on the core temperature response to a novel environment in pregnant rats

Fewell, James E., and Patricia A. Tang. Influence ofnicotine on the core temperature response to a novel environment inpregnant rats. J. Appl. Physiol.83(5): 1612-1616, 1997.Exposure of a male or nonpregnant femalerat to a novel environment, such as a simulated open field, induces atransient increase in core temperature, which is often calledstress-induced hyperthermia. Pregnancy alters this response such thatthe core temperature index increases significantly during exposure to asimulated open field on day 10 but noton days 15 and20 of gestation in rats. The presentexperiments were carried to investigate the effect of chronicadministration of nicotine (0, 1, 2, 4, or 8 mg · kg¹ · 24 h¹ for 13-15 days) onthe core temperature response to a simulated open field in chronicallyinstrumented pregnant (day 20 or21 of gestation) and nonpregnantSprague-Dawley rats. In nonpregnant rats, the core temperature indexincreased more during exposure to a simulated open field after chronicadministration of nicotine at all doses than after chronicadministration of vehicle; the core temperature response was notdependent on the dose of nicotine. In pregnant rats, significantincreases in core temperature as well as in the core temperature indexoccurred only during exposure to a simulated open field after chronicadministration of nicotine in doses of 2, 4, or 8 mg · kg¹ · 24 h¹; the core temperatureresponse was dependent on the dose of nicotine. Our data provideevidence that chronic exposure to nicotine enhances the coretemperature response to a simulated open field in nonpregnant rats andunmasks a maternal thermogenic response that is not seen to the samestimulus near term of pregnancy. The possible physiological consequences for the fetus are presently unknown and requireinvestigation.

     

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.

     

Appropriate thermal manipulations eliminate tremors in rats recovering from halothane anesthesia

Grahn, D. A., M. C. Heller, J. E. Larkin, and H. C. Heller.Appropriate thermal manipulations eliminate tremors in ratsrecovering from halothane anesthesia. J. Appl.Physiol. 81(6): 2547-2554, 1996.Tremors arecommon in mammals emerging from anesthesia. To determine whetherappropriate thermal manipulations immediately before emergence fromanesthesia are sufficient to eliminate these tremors,electroencephalographic (EEG) and electromyographic (EMG) activities,hypothalamic temperature (T_hy),and O₂ consumption were monitoredin 12 rats recovering from halothane anesthesia under three thermalregimes. EEG and EMG activities were recorded throughout anesthesia andserved as feedback signals for controlling anesthetic depth. Duringanesthesia, T_hy was either1) allowed to fall to32-34°C, 2) maintained at37-39°C, or 3) allowed to fall to 32-34°C and then raised to 37-39°C. Whenhypothermic on emergence from anesthesia, all of the animals exhibitedpostanesthetic tremors that persisted untilT_hy values returned tonormothermia. None of the animals expressed postanesthetic tremors whennormothermic on emergence from anesthesia. In addition, the timebetween emergence from anesthesia (as determined by EEG/EMG parameters)and the initiation of coordinated motor activities was significantlydecreased in the normothermic animals.

     

Acid-base regulation after maximal exercise testing in late gestation

Kemp, Justin G., Felicia A. Greer, and Larry A. Wolfe.Acid-base regulation after maximal exercise testing in late gestation. J. Appl. Physiol. 83(2):644-651, 1997.This study employed Stewart's physicochemicalapproach to quantify the effects of pregnancy and strenuous exercise onthe independent determinants of plasmaH⁺ concentration([H⁺]). Subjects werenine physically active pregnant women [mean gestational age = 33 ± 1 (SE) wk] and 14 age-matched nonpregnant controls. Venousblood samples and respiratory data were obtained at rest and during 15 min of recovery from a maximal cycle ergometer test that involved 20 W/min increases in work rate to exhaustion. Mean values for[H⁺],PCO₂, and total protein increased,whereas those for bicarbonate concentration([HCO₃]) and the strong ion difference ([SID]) decreased in the transition fromrest to maximal exercise within both groups. At rest and throughoutpostexercise recovery, the pregnant group exhibited significantly lowermean values for PCO₂,[HCO₃], and total protein,whereas [SID] was significantly lower at rest and early recovery from exercise.[H⁺] was also lower atall sampling times in the pregnant group, but this effect wassignificant only at rest. Our results support the hypothesis thatreduced PCO₂ and weak acidconcentration are important mechanisms to regulate plasma[H⁺] and to maintain aless acidic plasma environment at rest and after exercise in lategestation compared with the nonpregnant state. These effects areestablished in the resting state and appear to be maintained aftermaximal exertion.

     

Diaphragm thickening during inspiration

Cohn, David, Joshua O. Benditt, Scott Eveloff, and F. DennisMcCool. Diaphragm thickening during inspiration.J. Appl. Physiol. 83(1): 291-296, 1997.Ultrasound has been used to measure diaphragm thickness(T_di) in thearea where the diaphragm abuts the rib cage (zone of apposition).However, the degree of diaphragm thickening during inspiration reportedas obtained by one-dimensional M-mode ultrasound was greater than thatpredicted by using other radiographic techniques. Becausetwo-dimensional (2-D) ultrasound provides greater anatomic definitionof the diaphragm and neighboring structures, we used this technique toreevaluate the relationship between lung volume andT_di. We firstestablished the accuracy and reproducibility of 2-D ultrasound bymeasuring T_diwith a 7.5-MHz transducer in 26 cadavers. We found thatT_di measured byultrasound correlated significantly with that measured by ruler (R² = 0.89), withthe slope of this relationship approximating a line of identity(y = 0.89x + 0.04 mm). The relationship between lung volume andT_di was thenstudied in nine subjects by obtaining diaphragm images at the fivetarget lung volumes [25% increments from residual volume (RV) tototal lung capacity (TLC)]. Plots ofT_di vs. lungvolume demonstrated that the diaphragm thickened as lung volumeincreased, with a more rapid rate of thickening at the higher lungvolumes[T_di = 1.74 vital capacity (VC)² + 0.26 VC + 2.7 mm] (R² = 0.99; P < 0.001) where lung volumeis expressed as a fraction of VC. The mean increase inT_di between RVand TLC for the group was 54% (range 42-78%). We conclude that2-D ultrasound can accurately measureT_di and that theaverage thickening of the diaphragm when a subject is inhaling from RVto TLC using this technique is in the range of what would be predictedfrom a 35% shortening of the diaphragm.

     

Modification of active cutaneous vasodilation by oral contraceptive hormones

Charkoudian, Nisha, and John M. Johnson. Modificationof active cutaneous vasodilation by oral contraceptive hormones. J. Appl. Physiol. 83(6):2012-2018, 1997.It is not clear whether the alteredthermoregulatory reflex control of the cutaneous circulation seen amongphases of the menstrual cycle also occurs with the synthetic estrogenand progesterone in oral contraceptive pills and whether any suchmodifications include altered control of the cutaneous activevasodilator system. To address these questions, we conducted controlledwhole body heating experiments in seven women at the end of the thirdweek of hormone pills (HH) and at the end of the week of placebo/nopills (LH). A water-perfused suit was used to control body temperature.Laser Doppler flowmetry was used to monitor cutaneous blood flow at acontrol site and at a site at which noradrenergic vasoconstrictorcontrol had been eliminated by iontophoresis of bretylium (BT),isolating the active cutaneous vasodilator system. The oral temperature(T_or) thresholds for cutaneousvasodilation were higher in HH at both control [37.09 ± 0.12 vs. 36.83 ± 0.07°C (LH), P < 0.01] and BT-treated [37.19 ± 0.05 vs. 36.88 ± 0.12°C (LH), P < 0.01]sites. The T_or threshold forsweating was similarly shifted (HH: 37.15 ± 0.11°C vs. LH: 36.94 ± 0.11°C, P < 0.01). Arightward shift in the relationship of heart rate toT_or was seen in HH. Thesensitivities (slopes of the responses vs.T_or) did not differstatistically between phases. The similar threshold shifts at controland BT-treated sites suggest that the hormones shift the function ofthe active vasodilator system to higher internal temperatures. Thesimilarity of the shifts among thermoregulatory effectors suggests acentrally mediated action of these hormones.

     

Ventilatory and metabolic responses to ambient hypoxia or hypercapnia in rats exposed to CO hypoxia

Gautier, Henry, Cristina Murariu, and Monique Bonora.Ventilatory and metabolic responses to ambient hypoxia orhypercapnia in rats exposed to CO hypoxia. J. Appl. Physiol.83(1): 253-261, 1997.We have investigated at ambienttemperatures (T_am) of 25 and5°C the effects of ambient hypoxia(Hx_am; fractional inspired O₂ = 0.14) and hypercapnia(fractional inspiredCO₂ = 0.04) on ventilation (),O₂ uptake(O₂), andcolonic temperature (T_c) in 12 conscious rats before and after carotid body denervation (CBD). Therats were concomitantly exposed to CO hypoxia (Hx_CO; fractional inspired CO = 0.03-0.05%), which decreases arterial O₂ saturation by ~25-40%.The results demonstrate the following. 1) AtT_am of 5°C, in both intact andCBD rats,/O₂ islarger when Hx_am orCO₂ is associated withHx_CO than with normoxia. At T_am of 25°C, this is also thecase except for CO₂ in CBD rats. 2) AtT_am of 5°C, the changes inO₂ andT_c seem to result from additiveeffects of the separate changes induced byHx_am,CO₂, andHx_CO. It is concluded that, inconscious rats, central hypoxia does not depress respiratory activity.On the contrary, particularly whenO₂ is augmented during acold stress, both/O₂during Hx_CO and the ventilatoryresponses to Hx_am andCO₂ are increased. The mechanismsinvolved in this relative hyperventilation are likely to involvediencephalic integrative structures.

     

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.

     

Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise

González-Alonso, José, RicardoMora-Rodríguez, Paul R. Below, and Edward F. Coyle.Dehydration markedly impairs cardiovascular function inhyperthermic endurance athletes during exercise. J. Appl. Physiol. 82(4): 1229-1236, 1997.Weidentified the cardiovascular stress encountered by superimposingdehydration on hyperthermia during exercise in the heat and themechanisms contributing to the dehydration-mediated stroke volume (SV)reduction. Fifteen endurance-trained cyclists [maximalO₂ consumption(O_{2 max}) = 4.5 l/min] exercised in the heat for 100-120 min and either became dehydrated by 4% body weight or remained euhydrated by drinkingfluids. Measurements were made after they continued exercise at 71%O_{2 max} for 30 minwhile 1) euhydrated with anesophageal temperature (T_es) of38.1-38.3°C (control); 2)euhydrated and hyperthermic (39.3°C);3) dehydrated and hyperthermic withskin temperature (T_sk) of34°C; 4) dehydrated withT_es of 38.1°C and T_sk of 21°C; and5) condition4 followed by restored blood volume. Compared withcontrol, hyperthermia (1°C T_esincrease) and dehydration (4% body weight loss) each separatelylowered SV 7-8% (11 ± 3 ml/beat;P < 0.05) and increased heart ratesufficiently to prevent significant declines in cardiac output.However, when dehydration was superimposed on hyperthermia, thereductions in SV were significantly (P < 0.05) greater (26 ± 3 ml/beat), and cardiac output declined 13% (2.8 ± 0.3 l/min). Furthermore, mean arterialpressure declined 5 ± 2%, and systemic vascular resistanceincreased 10 ± 3% (both P < 0.05). When hyperthermia wasprevented, all of the decline in SV with dehydration was due to reducedblood volume (~200 ml). These results demonstrate that thesuperimposition of dehydration on hyperthermia during exercise in theheat causes an inability to maintain cardiac output and blood pressurethat makes the dehydrated athlete less able to cope with hyperthermia.

     

Effect of prior O2 breathing on ventilatory response to sustained isocapnic hypoxia in adult humans

Honda, Y., H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. Effect of priorO₂ breathing on ventilatoryresponse to sustained isocapnic hypoxia in adult humans.J. Appl. Physiol. 81(4):1627-1632, 1996.Sixteen healthy volunteers breathed 100%O₂ or room air for 10 min in random order, then their ventilatory response to sustained normocapnic hypoxia (80% arterial O₂saturation, as measured with a pulse oximeter) was studied for 20 min.In addition, to detect agents possibly responsible for the respiratorychanges, blood plasma of 10 of the 16 subjects was chemically analyzed.1) Preliminary O₂ breathing uniformly andsubstantially augmented hypoxic ventilatory responses.2) However, the profile ofventilatory response in terms of relative magnitude, i.e., biphasichypoxic ventilatory depression, remained nearly unchanged.3) Augmented ventilatory incrementby prior O₂ breathing wassignificantly correlated with increment in the plasma glutamine level.We conclude that preliminary O₂administration enhances hypoxic ventilatory response without affectingthe biphasic response pattern and speculate that the excitatory aminoacid neurotransmitter glutamate, possibly derived from augmentedglutamine, may, at least in part, play a role in this ventilatoryenhancement.

     

Ozone toxicity in the rat. III. Effect of changes in ambient temperature on pulmonary parameters

Wiester, Mildred J., William P. Watkinson, Daniel L. Costa,Kay M. Crissman, Judy H. Richards, Darrell W. Winsett, and Jerry W. Highfill. Ozone toxicity in the rat. III. Effect of changes inambient temperature on pulmonary parameters. J. Appl.Physiol. 81(4): 1691-1700, 1996.Pulmonarytoxicity of ozone (O₃) wasexamined in adult male Fischer 344 rats exposed to 0.5 parts/millionO₃ for either 6 or 23 h/day over 5 days while maintained at an ambient temperature(T_a) of either 10, 22, or34°C. Toxicity was evaluated by using changes in lung volumes andthe concentrations of constituents of bronchoalveolar lavage fluid thatsignal lung injury and/or inflammation. Results indicated thattoxicity increased as T_adecreased. Exposures conducted at 10°C were associated with thegreatest decreases in body weight and total lung capacity and thegreatest increases in lavageable protein, lysozyme, alkaline phosphatase activity, and percent neutrophils.O₃ effects not modified byT_a included increases in residualvolume and lavageable potassium, glucose, urea, and ascorbic acid.There was a progressive decrease in lavageable uric acid with exposureat 34°C. Most effects were attenuated during the 5 exposure daysand/or returned to normal levels after 7 air recovery days,regardless of prior O₃ exposure orT_a. It is possible thatT_a-induced changes in metabolic rate may have altered ventilation and, therefore, theO₃ doses among rats exposed at thethree different T_a levels.

     

Effect of episodic eucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats

Fletcher, Eugene C., and Gang Bao. Effect of episodiceucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats. J. Appl. Physiol. 81(5):2088-2094, 1996.Repetitive episodic (18-24 s twice perminute) hypocapnic hypoxia (HH) administered chronically (7 h/day, 35 days) to Sprague-Dawley or Wistar-Kyoto rats results in a sustainedincrease in daytime blood pressure (BP). We examined acute and chronicBP response to episodic HH and eucapnic hypoxia (EH) in borderlinehypertensive rats [first generation (F1) cross between spontaneouslyhypertensive and Wistar-Kyoto rats]. We hypothesized that episodic HHand EH would create a greater increase in acute and chronic BP in thisbreed of rat than in previously studied strains. We also examinedneural mechanisms by which BP changes from hypoxia are induced. BP andheart rate were examined acutely in nine F1 rats during baseline, HH,EH, EH with prazosin, and EH with prazosin and atropine. Five groups ofmale F1 rats were studied after 35-day exposure to the following: Unhandled (n = 8): no treatment; Sham (n = 10):episodic compressed air; HH (n = 14): daily episodic hypoxia(2.7%); EH1 (n = 12): hypoxia 2.9%, CO₂ 8.4%;and EH2 (n = 11): hypoxia 2.8% and CO₂ 10.5%.Under acute conditions, HH caused a 34.2-mmHg and EH a 77.9-mmHgincrease in mean BP. Prazosin partially blocked the increase in BP.Under chronic conditions, HH caused a 10.3-mmHg increase in daytimemean BP, whereas EH caused a fall in mean BP of 16.6 and 9.3 mmHg inthe two separately studied groups. In the F1 rat, acute EH causes anelevation of BP but chronic EH causes a fall in BP. The acute responseto EH is not predictive of what occurs after chronic exposure in thehypertension-prone F-1 rat.

     

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.

     

In vitro bronchial responsiveness in two highly inbred rat strains

Wang, C. G., J. J. Almirall, C. S. Dolman, R. J. Dandurand,and D. H. Eidelman. In vitro bronchial responsiveness in twohighly inbred rat strains. J. Appl.Physiol. 82(5): 1445-1452, 1997.We investigatedmethacholine (MCh)-induced bronchoconstriction in explanted airwaysfrom Fischer and Lewis rats. Lung explants, 0.5- to 1.0-mm thick, wereprepared from agarose-inflated lungs of anesthetized 8- to 12-wk-oldmale rats. After overnight culture, videomicroscopy was used to recordbaseline images of the individual airways. Dose-response curves to MChwere then constructed by repeated administration of MCh; airways werereimaged 10 min after each MCh administration. Airway internal luminalarea(A_i)was measured at successive MCh concentrations from10⁹ to10¹ M. Inaddition to the effective concentration leading to 50% of the achievedmaximal response, we also determined the effective concentrationleading to a 40% reduction inA_i.Both the effective concentration leading to 50% of the achievedmaximal response and the concentration leading to a 40% reduction inA_iwere significantly lower among Fischer rat airways(P < 0.05). Airway closure was morecommon among Fischer rat airways (17%) than among those of Lewis rats(7.5%). Responsiveness of Fischer rat airways was more heterogeneousthan among Lewis airways; a larger number of Fischer rat airwaysexhibited high sensitivity to MCh. There was no relationship betweenresponsiveness and baselineA_iin either strain. In a second experiment, we measured the rate ofcontraction of explanted airways from lungs inflated to 50, 75, and100% of total lung capacity. The average rate of contraction in thefirst 15 s was higher in Fischer rat airways at each inflation volume.These data indicate that the hyperresponsiveness of the Fischer rat reflects the responsiveness of individual airways throughout the airwaytree and are consistent with the notion that in this model hyperresponsiveness is an intrinsic property of airway smooth 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.

     

Posthemorrhagic antipyresis: what stage of fever genesis is affected?

Romanovsky, Andrej A., and Yelena K. Karman.Posthemorrhagic antipyresis: what stage of fever genesis isaffected? J. Appl. Physiol. 83(2):359-365, 1997.It has been shown that hemorrhage leads to adecreased thermal responsiveness to lipopolysaccharide (LPS). The aimof this study was to clarify what stage of fever genesis[production of endogenous pyrogens such as interleukin-1 (IL-1),increase of the prostaglandin E₂(PGE₂) concentration in braintissue, activation of cold-defense effectors] is deficient inposthemorrhagic antipyresis. In adult rabbits, we evaluated the effectof acute hemorrhage (15 ml/kg) on the rectal temperature (T_re) responses to LPS fromSalmonella typhi (200 ng/kg iv),ethanol-purified preparation of homologous IL-1 (1 ml from 3.5 × 10⁷ cells, 1.5 ml/kg iv), andPGE₂ (1 µg,intracisternal injection). The effect of hemorrhage onT_re was also studied in afebrilerabbits, both at thermoneutrality (23°C) and during ramp cooling(to 7°C). The hemorrhage strongly attenuated the biphasicLPS-induced fever (a T_re rise of0.4 ± 0.1 instead of 1.2 ± 0.2°C at the time of the secondpeak), the monophasic T_re responseto IL-1 (by ~0.5°C for over 1-5 h postinjection), and thePGE₂-induced hyperthermia (0.4 ± 0.1 vs. 0.9 ± 0.1°C, maxima). In afebrileanimals, the hemorrhage neither affectedT_re at thermoneutrality norchanged the T_re response to coldexposure. The data suggest that neither insufficiency of cold-defenseeffectors nor lack of endogenous mediators of fever (IL-1,PGE₂) can be the only or eventhe major cause of posthemorrhagic antipyresis. Wespeculate that fever genesis is altered at a stage occurring after theintrabrain PGE₂ level is increasedbut before thermoeffectors are activated.