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.

     

Role of AVP in mediating the altered core temperature response to a simulated open field in pregnant rats.

Near the term of pregnancy, rats have an attenuated core temperature response on exposure to a novel environment (e.g., a simulated open field) compared with that observed early in pregnancy or in nonpregnant rats. The present experiments were carried out on 26 nonpregnant and 26 pregnant rats to test the hypothesis that arginine vasopressin, functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated core temperature response. Exposure to a simulated open field after intracerebroventricular (ICV) vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which were greater in the nonpregnant rats. In nonpregnant rats, exposure to a simulated open field after ICV vasopressin V(1)-receptor antagonist altered the pattern of the core temperature response but not the core temperature index compared with that observed on exposure to a simulated open field after ICV vehicle. In pregnant animals, ICV vasopressin V(1)-receptor antagonist did not alter the core temperature response to a simulated open field compared with that observed after ICV vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin attenuates the core temperature response to a simulated open field in rats near the term of pregnancy.     

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.

     

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.

     

Stress-induced hyperthermia is not mediated by brown adipose tissue in mice

Psychological stress leads to sympathetically mediated increases in body temperature. Brown adipose tissue (BAT) is often thought to be the main organ to produce heat in response to sympathetic activation. However, we have previously shown that the hyperthermia evoked by conditioned fear in rats is not the result of thermogenesis in the interscapular area of the back, where the largest deposit of BAT is found. Stress-induced hyperthermia is widely used as an anxiety indicator in mice. We thus sought to verify if this response can be attributed to BAT thermogenesis. Eight C57BL/6 mice were shaved in the interscapular and lumbar back areas prior to testing. Animals received injections of 20 mg/kg dl-propranolol or saline and were placed in either an open field or 4 °C enclosure for 30 min. Infrared thermographic images were taken each minute to record interscapular, lumbar and tail skin temperatures. Propranolol reduced the stress-induced hyperthermia observed during open field exposure (p<0.01), as indicated by the lumbar back skin temperature. Nevertheless, the difference between interscapular and lumbar skin temperatures remained constant, suggesting that this hyperthermia was not caused by BAT thermogenesis. There was no observable effect of propranolol on behavior, as animals remained active throughout the test. In contrast, the difference between interscapular and lumbar back skin temperature was increased by 2 °C during cold exposure. This increase was abolished after propranolol (p<0.001), indicating BAT thermogenesis during this challenge. Hence, just as rats exposed to conditioned fear, mice exposed to an open field display a stress-induced hyperthermia that is not caused by BAT thermogenesis.     

Reflex apneic response evoked by laryngeal exposure to wood smoke in rats: neural and chemical mechanisms

Lin, Y. S., and Y. R. Kou. Reflex apneic responseevoked by laryngeal exposure to wood smoke in rats: neural and chemical mechanisms. J. Appl. Physiol. 83(3):723-730, 1997.We investigated the neural and chemical mechanismscontributing to the immediate ventilatory responses to laryngealexposure to wood smoke in anesthetized Sprague-Dawley rats. Fivemilliliters of wood smoke were delivered into a functionally isolatedlarynx at a constant flow rate of 1.4 ml/s while the animals breathedspontaneously. Within 1 s after exposure, laryngeal wood smokeconsistently triggered an apnea in each of the 42 rats tested. Theapneic duration reached 1,636.4 ± 105.4 (SE) % (n = 42) of the baseline expiratoryduration. This apneic response was not affected by denervation ofrecurrent laryngeal nerves (n = 6) orby removal of smoke particulates (n = 14), but it was totally eliminated by topical application of ananesthetic (n = 8; lidocainehydrochloride, 8%) to the laryngeal mucosa or by sectioning of thesuperior laryngeal nerves (n = 42).Furthermore, laryngeal application of a hydroxyl radical scavenger(dimethylthiourea; 500 mg/ml; n = 8)greatly diminished or abolished the smoke-induced apneic response, butit did not affect the apneic response evoked by laryngeal exposure toair saturated with 6% ammonia. These results suggest that theimmediate apneic response to laryngeal wood smoke is a reflex resulting from the stimulation of the superior laryngeal afferents by the gasphase of wood smoke and that the stimulation is mediated through ahydroxyl radical mechanism.

     

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 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.

     

Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia

Roach, Robert C., Jack A. Loeppky, and Milton V. Icenogle.Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia. J. Appl.Physiol. 81(5): 1908-1910, 1996.Acute mountainsickness (AMS) strikes those in the mountains who go too high too fast.Although AMS has been long assumed to be due solely to the hypoxia ofhigh altitude, recent evidence suggests that hypobaria may also make asignificant contribution to the pathophysiology of AMS. We studied ninehealthy men exposed to simulated altitude, normobaric hypoxia, andnormoxic hypobaria in an environmental chamber for 9 h on separateoccasions. To simulate altitude, the barometric pressure was lowered to432 ± 2 (SE) mmHg (simulated terrestrial altitude 4,564 m).Normobaric hypoxia resulted from adding nitrogen to the chamber(maintained near normobaric conditions) to match the inspiredPO₂ of the altitude exposure. Bylowering the barometric pressure and adding oxygen, we achievednormoxic hypobaria with the same inspiredPO₂ as in our laboratory at normalpressure. AMS symptom scores (average scores from 6 and 9 h ofexposure) were higher during simulated altitude (3.7 ± 0.8)compared with either normobaric hypoxia (2.0 ± 0.8;P < 0.01) or normoxic hypobaria (0.4 ± 0.2; P < 0.01). In conclusion,simulated altitude induces AMS to a greater extent than does eithernormobaric hypoxia or normoxic hypobaria, although normobaric hypoxiainduced some AMS.

     

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.

     

Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

Marsh, Daniel R., David S. Criswell, James A. Carson, andFrank W. Booth. Myogenic regulatory factors during regeneration ofskeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270-1275, 1997.Myogenicfactor mRNA expression was examined during muscle regeneration afterbupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of thetibialis anterior muscle in the young rats had recovered to controlvalues by 21 days postbupivacaine injection but in adult and old ratsremained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA wassignificantly increased in muscles of young, adult, and old rats 5 daysafter bupivacaine injection. Subsequently, myogenin mRNA levels inyoung rat muscle decreased to postinjection control values byday 21 but did not return to controlvalues in 28-day regenerating muscles of adult and old rats. Theexpression of MyoD mRNA was also increased in muscles atday 5 of regeneration in young, adult,and old rats, decreased to control levels by day14 in young and adult rats, and remained elevated inthe old rats for 28 days. In summary, either a diminished ability todownregulate myogenin and MyoD mRNAs in regenerating muscle occurs inold rat muscles, or the continuing myogenic effort includes elevatedexpression of these mRNAs.

     

Reduction in open field-induced hyperthermia in the rat exposed to chlorpyrifos,an anticholinesterase pesticide

Rodents develop a marked elevation in core temperature (T_c) when they are placed in an open field environment (OFE). Open field-induced hyperthermia (OFH) involves activation of thermoregulatory systems that are quiescent under baseline conditions. Cholinergic stimulation arising from exposure to organophosphates (OP) is expected to modulate OFH; subtle effects of OPs may be observed during OFH that would not occur in the absence of stress. We have found that methyl scopolamine (MS), a peripheral muscarinic antagonist, attenuates stress-induced hyperthermia. To this end, we assessed if a low dose of the OP pesticide chlorpyrifos (CHP) would alter OFH with and without administration of MS. T_c and motor activity (MA) of male, Sprague-Dawley rats were monitored by telemetry while housed in their home cage at an ambient temperature of 22°C. At 9 AM the rats were gavaged with corn oil or 10 mg/kg CHP that resulted in a ∼40% inhibition in plasma cholinesterase activity. T_c and MA were the same in the control and CHP groups prior to OFE. The rats were then dosed IP with saline or 1.0 mg/kg MS at 12 noon and subjected to OFE (61×61×61 cm box) for 1 h while T_c and MA were monitored every 2 min. T_c of the corn oil/saline group increased by 1.2°C during OFE, whereas T_c of the CHP/saline group was significantly attenuated. Administration of MS attenuated the OFH in rats treated with corn oil and CHP. Overall, exposure to OFE exacerbated the effects of a relatively low dose of CHP that had no effect in the unstressed animal. In addition, the OFH response to MS suggests a peripheral (i.e., outside of CNS) cholinergic pathway is operative in the control of OFH.     

Influence of treadmill running on femoral bone in young orchidectomized rats

Horcajada, M.-N., V. Coxam, M.-J. Davicco, N. Gaumet, P. Pastoureau, C. Leterrier, J. Culioli, and J.-P. Barlet. Influence of treadmill running on femoral bone in young orchidectomized rats.J. Appl. Physiol. 83(1): 129-133, 1997.Forty 6-wk-old male Wistar rats weighing 308 ± 24 g weredivided into two groups. On day 0, the20 animals in one group were surgically castrated and the other groupwas sham operated. Within each group, 10 rats were selected fortreadmill running (60% maximal O₂consumption, 1 h/day, 6 days/wk for 15 wk). The 20 sedentary rats wereused as controls. At the time the rats were killed(day 105), running had nosignificant effect on femoral mechanical properties either in castratedor in sham-operated rats. Femoral bone density was lowerin orchidectomized than in sham-operated rats. Nevertheless, it washigher in exercised than in sedentary rats. Femoral Ca contentparalleled changes in bone density. Treadmill running had nosignificant effect on plasma osteocalcin concentration but inhibitedthe increase in urinary deoxypyridinoline excretion observed incastrated rats. Image analysis (measured at the distal femoraldiaphysis) revealed that these effects mainly resulted from decreasedtrabecular bone resorption in castrated exercised rats.

     

Body and brain temperature coupling: the critical role of cerebral blood flow

Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; α-chloralose, αCS; and isoflurane, IF) with αCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO₂ in 40% O₂ and 55% N₂). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under αCS anesthesia (ca. 2°C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials—αCS anesthesia resulted in the largest brain temperature increase (0.32 ± 0.08°C), while CH and IF anesthesia lead to smaller increases (0.12 ± 0.03 and 0.16 ± 0.05°C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2–3 min under CH and IF anesthesia and ~4 min under αCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures.     

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.

     

Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness

Colice, Gene L., Nicholas Hill, Yan-Jie Lee, Hongkai Du,James Klinger, James C. Leiter, and Lo-Chang Ou. Exaggerated pulmonary hypertension with monocrotaline in rats susceptible tochronic mountain sickness. J. Appl.Physiol. 83(1): 25-31, 1997.Hilltop (H) strainSprague-Dawley rats are more susceptible to chronic mountain sicknessthan are the Madison (M) strain rats. It is unclear what role pulmonaryvascular remodeling, polycythemia, and hypoxia-induced vasoconstrictionplay in mediating the more severe pulmonary hypertension that developsin the H rats during chronic hypoxia. It is also unclear whether theincreased sensitivity of the H rats to chronic mountain sickness isspecific for a hypoxia effect or, instead, reflects a generalpropensity toward the development of pulmonary hypertension.Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonaryhypertension. We hypothesized that the difference in the pulmonaryvascular response to chronic hypoxia between H and M rats reflects anincreased sensitivity of the H rats to any pulmonary hypertensivestimuli. Consequently, we expected the two strains to also differ intheir susceptibility to MCT-induced pulmonary hypertension. Pulmonaryarterial pressures in conscious H and M rats were measured 3 wk after asingle dose of MCT, exposure to a simulated high altitude of 18,000 ft(barometric pressure = 380 mmHg), and administration of a single doseof saline as a placebo. The H rats had significantlyhigher pulmonary arterial pressures and right ventricular weights afterMCT and chronic hypoxia than did the M rats. The H rats also had morepulmonary vascular remodeling, i.e., greater wall thickness as apercentage of vessel diameter, after MCT and chronic hypoxia than didthe M rats. The H rats had significantly lower arterialPO₂ than did the M rats after MCT,but the degree of hypoxemia was mild [arterialPO₂ of 72.5 ± 0.8 (SE) Torr for Hrats vs. 77.4 ± 0.8 Torr for M rats after MCT]. The H ratshad lower arterial PCO₂ and largerminute ventilation values than did the M rats after MCT. Theseventilatory differences suggest that MCT caused more severe pulmonaryvascular damage in the H rats than in the M rats. These data supportthe hypothesis that the H rats have a general propensity to developpulmonary hypertension and suggest that differences in pulmonaryvascular remodeling account for the increased susceptibility of H rats,compared with M rats, to both MCT and chronic hypoxia-induced pulmonaryhypertension.

     

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.

     

Simulation of motor unit recruitment and microvascular unit perfusion: spatial considerations

Fuglevand, Andrew J., and Steven S. Segal. Simulationof motor unit recruitment and microvascular unit perfusion: spatial considerations. J. Appl. Physiol.83(4): 1223-1234, 1997.Muscle fiber activity is the principalstimulus for increasing capillary perfusion during exercise. Thecontrol elements of perfusion, i.e., microvascular units (MVUs), supplyclusters of muscle fibers, whereas the control elements of contraction,i.e., motor units, are composed of fibers widely scattered throughoutmuscle. The purpose of this study was to examine how the discordantspatial domains of MVUs and motor units could influence the proportion of open capillaries (designated as perfusion) throughout a muscle crosssection. A computer model simulated the locations of perfused MVUs inresponse to the activation of up to 100 motor units in a muscle with40,000 fibers and a cross-sectional area of 100 mm². The simulation increasedcontraction intensity by progressive recruitment of motor units. Foreach step of motor unit recruitment, the percentage of active fibersand the number of perfused MVUs were determined for several conditions:1) motor unit fibers widely dispersed and motor unit territories randomly located (whichapproximates healthy human muscle),2) regionalized motor unitterritories, 3) reversed recruitmentorder of motor units, 4) denselyclustered motor unit fibers, and 5)increased size but decreased number of motor units. The simulationsindicated that the widespread dispersion of motor unit fibersfacilitates complete capillary (MVU) perfusion of muscle at low levelsof activity. The efficacy by which muscle fiber activity inducedperfusion was reduced 7- to 14-fold under conditions that decreased thedispersion of active fibers, increased the size of motor units, orreversed the sequence of motor unit recruitment. Such conditions aresimilar to those that arise in neuromuscular disorders, with aging, orduring electrical stimulation of muscle, respectively.

     

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

     

Protoveratrines A and B increase sleep apnea index in Sprague-Dawley rats

Trbovic, Sinisa M., Miodrag Radulovacki, and David W. Carley. Protoveratrines A and B increase sleep apneaindex in Sprague-Dawley rats. J. Appl.Physiol. 83(5): 1602-1606, 1997.The action ofprotovertarines A and B, which stimulate carotid sinus baroreceptorsand vagal sensory endings in the heart as well as pulmonary bed, wereassessed on spontaneous and postsigh central sleep apneas in freelymoving Sprague-Dawley rats. During the 6-h recording period, animalswere simultaneously monitored for sleep by using electroencephalogramand electromyogram recordings, for respiration by single-chamberplethysmography, and for blood pressure and heart period by usingradiotelemetry. After administration of 0.2, 0.5, or 1 mg/kg sc ofprotoveratrines, cardiopulmonary changes lasting at least 6 h wereobserved in all three behavioral states [heart period increasedup to 23% in wakefulness, 21% in non-rapid-eye-movement (non-REM)sleep, and 20% in REM sleep; P < 0.005 for each]. At the same time, there was a substantial increase in the number of spontaneous (375% increase;P = 0.04) and postsigh (268%increase, P = 0.0002) apneas. Minuteventilation decreased by up to 24% in wakefulness, 25% in non-REM,and 35% in REM sleep (P < 0.05 foreach). We conclude that pharmacological stimulation of baroreflexespromotes apnea expression in the sleeping rat.