Alterations in structure of elastic laminae of rat pulmonary arteries in hypoxic hypertension

Liu, S. Q. Alterations in structure of elastic laminaeof rat pulmonary arteries in hypoxic hypertension. J. Appl. Physiol. 81(5): 2147-2155, 1996.The effectof hypoxic hypertension on the remodeling process of the elasticlaminae of the rat hilar pulmonary arteries (PAs) was studied byelectron microscopy. Rats were exposed to hypoxia (10%O₂) for periods of 0.5, 2, 6, 12, 48, 96, 144, and 240 h. Changes in the structure of the PA elastic laminae were examined and analyzed with respect to changes in the PAwall tensile stress. The PA blood pressure increased rapidly within thefirst several hours of hypoxia and reached a stable level within 2 days, whereas the PA wall tensile stress increased initially due toelevated blood pressure and then decreased after 48 h due to vesselwall thickening and returned to the control level after 4 days. Inassociation with these changes, the elastic laminae, which appearedhomogeneous in normal control rats, changed into structures composed ofrandomly oriented filaments and edematous contents with an increase inthe volume during the early period of hypoxia and regained theirhomogeneous appearance and normal volume after 4 days. The changes inthe elastic laminae were correlated with changes in the tensile stress.These changes were associated with a transient decrease in thestiffness of the PAs. In hypoxic rats given nifedipine, no change wasfound in the blood pressure, the tensile stress, or the structure ofthe elastic laminae of the PAs despite continuous exposure to hypoxia.These results suggested that altered tensile stress in the PA wallplayed a critical role in the initiation and regulation of structuralchanges in the elastic laminae and that these changes might contribute to alterations in the mechanical properties of the PA in hypoxic hypertension.

     

Nonspecific endothelin-receptor antagonist blunts monocrotaline-induced pulmonary hypertension in rats

Hill, Nicholas S., Rod R. Warburton, Linda Pietras, andJames R. Klinger. Nonspecific endothelin-receptor antagonist blunts monocrotaline-induced pulmonary hypertension in rats.J. Appl. Physiol. 83(4):1209-1215, 1997.Endothelin-1 (ET-1), a potent vasoactive andmitogenic peptide, has been implicated in the pathogenesis ofseveral forms of pulmonary hypertension. We hypothesized thatnonspecific blockade of ET receptors would blunt the development ofmonocrotaline (MCT)-induced pulmonary hypertension in rats. Asingle dose of the nonspecific ET blocker bosentan (100 mg/kg) given tointact rats by gavage completely blocked the pulmonary vasoconstrictoractions of Big ET-1 and partially blunted hypoxic pulmonaryvasoconstriction. After 3 wk, MCT-injected (105 mg/kg sc) rats gavagedonce daily with bosentan (200 mg/kg) had lower right ventricular (RV)systolic pressure (RVSP), RV-to-body weight (RV/BW) andRV-to-left ventricular (LV) plus septal (S) weight [RV/(LV+S)] ratiosand less percent medial thickness of small pulmonary arteries thancontrol MCT-injected rats. Lower dose bosentan (100 mg/kg) had noeffect on these parameters after MCT or saline injection. Bosentanraised plasma ET-1 levels but had no effect on lung ET-1 levels.Bosentan (200 mg/kg) also had no effect on wet-to-dry lung weightratios 6 days after MCT injection. When given during the last 10 days,but not the first 11 days of a 3-wk period after MCT injection,bosentan reduced RV/(LV+S) compared with MCT-injected controls. Weconclude that ET-1 contributes to the pathogenesis of MCT-inducedpulmonary hypertension and acts mainly during the later inflammatoryrather than the acute injury phase after injection.

     

Chronic hypoxia alters nitric oxide-dependent pulmonary vascular responses in lungs of newborn pigs

Fike, Candice D., and Mark R. Kaplowitz. Chronichypoxia alters nitric oxide-dependent pulmonary vascular responses inlungs of newborn pigs. J. Appl.Physiol. 81(5): 2078-2087, 1996.Almost all ofthe studies evaluating the effect of chronic hypoxia on lung nitricoxide production have been performed in adult animals. Because resultsof studies in adult lungs should not be extrapolated to represent thenewborn lung, we performed studies to determine whether decreasednitric oxide production might be involved in the pathogenesis ofchronic hypoxia-induced pulmonary hypertension in newborns. We keptnewborn pigs in chambers filled with room air (control) or 11-12%O₂ for either 3-5 (short) or10-12 (long) days. Using isolated lungs, we measured pulmonary vascular responses to agents that either stimulate or inhibit thesynthesis of nitric oxide. To define the vascular sites of alteredproduction of nitric oxide, we applied the micropuncture technique andmeasured small venular pressures before and after treatment with anitric oxide synthesis inhibitor. Pulmonary vascular responses toacetylcholine were blunted in chronically hypoxic piglets of both theshort and long groups. The nitric oxide synthesis inhibitor had adifferent effect in the lungs of control piglets than in those ofchronically hypoxic piglets of the long but not of the short group. Forthe long group, the nitric oxide synthesis inhibitors causedconstriction of both arteries and veins in lungs of control but not ofchronically hypoxic piglets. These findings support the idea thatdecreased pulmonary vascular nitric oxide production occurs withchronic hypoxia in newborn pigs and might therefore contribute to thepathogenesis of pulmonary hypertension in newborns.

     

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.

     

Normal forces and myofibrillar disruption after repeated eccentric exercise

Hortobágyi, Tibor, Joseph Houmard, David Fraser,Ronald Dudek, Jean Lambert, and James Tracy. Normalforces and myofibrillar disruption after repeated eccentric exercise.J. Appl. Physiol. 84(2): 492-498, 1998.To investigate the "rapid-adaptation" phenomenon, weexamined force, neural, and morphological adaptations in 12 subjectswho performed 100 eccentric contractions with the quadriceps muscle(bout 1) and repeated the sameexercise after a 2-wk hiatus (bout2). Two days after bout1, quadriceps muscle strength and surfaceelectromyographic (EMG) activity declined ~37 and 28%, respectively,in the control group (n = 6). Atday 2 after bout 1, significant increases occurred in patellar tendonreflex amplitude (~25%), muscle soreness (fivefold), and serumcreatine kinase (220%), and 65 ± 12% of the total number of pixelsin the EMG indicated myofibrillar disruption. At day7 after bout 1, all variables returned to normal. At day 2 after bout 2, no significant changesoccurred in force, EMG, creatine kinase, or soreness, but reflexamplitude increased, and 23 ± 4% of the total number of pixels inthe EMG still indicated myofibrillar disruption. The results suggestthat the rapid force recovery following eccentric exercise is mediatedat least in part by neural factors and that this recovery may occurindependently of cell disruption.

     

Effect of leucine metabolite beta -hydroxy-beta -methylbutyrate on muscle metabolism during resistance-exercise training

Nissen, S., R. Sharp, M. Ray, J. A. Rathmacher, D. Rice, J. C. Fuller, Jr., A. S. Connelly, and N. Abumrad. Effect of leucinemetabolite -hydroxy--methylbutyrate on muscle metabolism duringresistance-exercise training. J. Appl.Physiol. 81(5): 2095-2104, 1996.The effects ofdietary supplementation with the leucine metabolite-hydroxy--methylbutyrate (HMB) were studied in two experiments.In study 1, subjects(n = 41) were randomized among threelevels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two proteinlevels (normal, 117 g/day, or high, 175 g/day) and weight lifted for1.5 h 3 days/wk for 3 wk. In study 2,subjects (n = 28) were fed either 0 or3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 wk. Instudy 1, HMB significantly decreased the exercise-induced rise in muscle proteolysis as measured by urine3-methylhistidine during the first 2 wk of exercise (linear decrease,P < 0.04). Plasma creatinephosphokinase was also decreased with HMB supplementation(week 3, linear decrease,P < 0.05). Weight lifted wasincreased by HMB supplementation when compared with the unsupplementedsubjects during each week of the study (linear increase,P < 0.02). In study2, fat-free mass was significantly increased inHMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 wk of the study (P < 0.05). In conclusion, supplementation with either 1.5 or 3 g HMB/daycan partly prevent exercise-induced proteolysis and/or muscledamage and result in larger gains in muscle function associated withresistance training.

     

Changes in leg vein filling and emptying characteristics and leg volumes during long-term head-down bed rest

Louisy, Francis, Philippe Schroiff, and Antonio Güell.Changes in leg vein filling and emptying characteristics and legvolumes during long-term head-down bed rest. J. Appl.Physiol. 82(6): 1726-1733, 1997.Leg venoushemodynamics [venous distensibility index (VDI), arterial flowindex (AFI), half-emptying time(T_1/2)], and leg volumes(LV) were assessed by mercury strain-gauge plethysmography with venousocclusion and volometry, respectively, in seven men before, during, andafter 42 days of 6° head-down bed rest. Results showed a highincrease in VDI up to day 26 of bedrest (+50% vs. control at day 26,P < 0.05), which tended to subsidethereafter (+20% increase vs. control value at day41, P < 0.05). VDIchanges were associated with parallel changes inT_1/2 (+54% vs. control atday 26 of bed rest,P < 0.05, and +25% vs.control at day 41, P < 0.05) and with a decrease in AFI(49% at day 41 vs. control, P < 0.05). LV continuously decreasedthroughout bed rest (13% vs. control at day41, P < 0.05) but was correlated with VDI only during the first month ofbed rest. These results show that during long-term 6° head-down bedrest alterations of leg venous compliance are associated withimpairment of venous emptying capacities and arterial flow. Changes inskeletal muscle mass and fluid shifts may account for venous changesduring the first month of bed rest but, subsequently, otherphysiological factors, to be determined, may also be involved in legvenous hemodynamic alterations.

     

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.

     

Cardiovascular adaptations to 10days of cycle exercise

Mier, Constance M., Michael J. Turner, Ali A. Ehsani, andRobert J. Spina. Cardiovascular adaptations to 10 days of cycleexercise. J. Appl. Physiol. 83(6):1900-1906, 1997.We hypothesized that 10 days of training wouldenhance cardiac output (CO) and stroke volume (SV) during peak exerciseand increase the inotropic response to -adrenergic stimulation. Tensubjects [age 26 ± 2 (SE) yr] trained on a cycleergometer for 10 days. At peak exercise, training increasedO₂ uptake, CO, and SV(P < 0.001). Left ventricular (LV)size and function at rest were assessed with two-dimensional echocardiography before (baseline) and after atropine injection (1.0 mg) and during four graded doses of dobutamine. LV end-diastolic diameter increased with training (P < 0.02), whereas LV wall thickness was unchanged. LV contractileperformance was assessed by relating fractional shortening (FS) to theestimated end-systolic wall stress(_ES). Training increased theslope of the FS-_ES relationship (P < 0.05), indicating enhancedsystolic function. The increase in slope correlated with increases inCO (r = 0.71,P < 0.05) and SV(r = 0.70,P < 0.05). The increase in bloodvolume also correlated with increases in CO(r = 0.80, P < 0.01) and SV (r = 0.85, P < 0.004). These datashow that 10 days of training enhance the inotropic response to-adrenergic stimulation, associated with increases in CO and SVduring peak exercise.

     

Short-term exercise training alters responses of porcine femoral and brachial arteries

McAllister, Richard M., and M. Harold Laughlin.Short-term exercise training alters responses of porcine femoraland brachial arteries. J. Appl.Physiol. 82(5): 1438-1444, 1997.The primarypurpose of this study was to test the hypothesis that short-termexercise training enhances endothelium-dependent relaxation of porcinefemoral and brachial arteries. Miniature swine ran on a treadmill for 1 h at 3.5 miles/h, twice daily, for 7 consecutive days (Trn;n = 8). Compared with sedentarycontrols (Sed; n = 7), Trn swineexhibited increased skeletal muscle citrate synthase activity(P < 0.05). Vascular rings ~3 mmin axial length were prepared from segments of femoral and brachialarteries, and responses to vasoactive agents were determined in vitro.Sensitivity to bradykinin (BK) was enhanced in brachial vascular ringsfrom Trn swine compared with those from Sed swine, as indicated bylower concentration of vasorelaxing agent eliciting 50% of maximalresponse values [Sed, 8.63 ± 0.09 (log M); Trn, 9.07 ± 0.13; P < 0.05]. Thisdifference between groups was preserved in brachial rings in whichformation of nitric oxide and vasodilator prostaglandins were inhibited[Sed, 8.57 ± 0.17 (log M); Trn, 8.97 ± 0.13;P < 0.05]. Sensitivity to BKwas not different between Sed and Trn in femoral arterial rings.Relaxation responses to the calcium ionophore A-23187 and sodiumnitroprusside were not altered with training. Femoral and brachialarterial rings from Trn swine, compared with those from Sed swine,exhibited augmented vasocontraction across a range of concentrationsand increased sensitivity to norepinephrine (allP < 0.05). These findings indicatethat responses of porcine femoral and brachial arteries change inresponse to short-term training. Together with findings from previousstudies involving longer term training, our data suggest that vascular adaptations may differ at different time points during long-term endurance exercise training.

     

Long-term creatine intake is beneficial to muscle performance during resistance training

Vandenberghe, K., M. Goris, P. Van Hecke, M. Van Leemputte,L. Vangerven, and P. Hespel. Long-term creatine intake isbeneficial to muscle performance during resistance training. J. Appl. Physiol. 83(6):2055-2063, 1997.The effects of oral creatine supplementation onmuscle phosphocreatine (PCr) concentration, muscle strength, and bodycomposition were investigated in young female volunteers(n = 19) during 10 wk ofresistance training (3 h/wk). Compared with placebo, 4 days ofhigh-dose creatine intake (20 g/day) increased(P < 0.05) muscle PCr concentration by 6%. Thereafter, this increase was maintained during 10 wk of training associated with low-dose creatine intake (5 g/day).Compared with placebo, maximal strength of the muscle groups trained,maximal intermittent exercise capacity of the arm flexors, and fat-free mass were increased 20-25, 10-25, and 60% more(P < 0.05), respectively, duringcreatine supplementation. Muscle PCr and strength, intermittent exercise capacity, and fat-free mass subsequently remained at a higherlevel in the creatine group than in the placebo group during 10 wk ofdetraining while low-dose creatine was continued. Finally, on cessationof creatine intake, muscle PCr in the creatine group returned to normalwithin 4 wk. It is concluded that long-term creatine supplementationenhances the progress of muscle strength during resistance training insedentary females.

     

Effect of chronic resistive loading on hypoxic ventilatory responsiveness

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

     

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.

     

Effects of concentric and eccentric training on muscle strength, cross-sectional area, and neural activation

Higbie, Elizabeth J., Kirk J. Cureton, Gordon L. Warren III,and Barry M. Prior. Effects of concentric and eccentric trainingon muscle strength, cross-sectional area, and neural activation.J. Appl. Physiol. 81(5):2173-2181, 1996.We compared the effects of concentric (Con) andeccentric (Ecc) isokinetic training on quadriceps muscle strength,cross-sectional area, and neural activation. Women (age 20.0 ± 0.5 yr) randomly assigned to Con training (CTG;n = 16), Ecc training (ETG;n = 19), and control (CG;n = 19) groups were tested before andafter 10 wk of unilateral Con or Ecc knee-extension training. Averagetorque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8% for CTG, 6.8 and 36.2% for ETG, and 4.7 and1.7% for CG, respectively. Increases by CTG and ETG were greater than for CG (P < 0.05). ForCTG, the increase was greater when measured with Con than with Ecctesting. For ETG, the increase was greater when measured with Ecc thanwith Con testing. The increase by ETG with Ecc testing was greater thanthe increase by CTG with Con testing. Corresponding changes in theintegrated voltage from an electromyogram measured during strengthtesting were 21.7 and 20.0% for CTG, 7.1 and 16.7% for ETG, and8.0 and 9.1% for CG. Quadriceps cross-sectional areameasured by magnetic resonance imaging (sum of 7 slices) increased morein ETG (6.6%) than in CTG (5.0%) (P < 0.05). We conclude that Ecc is more effective than Con isokinetictraining for developing strength in Ecc isokinetic muscle actions andthat Con is more effective than Ecc isokinetic training for developingstrength in Con isokinetic muscle actions. Gains in strength consequentto Con and Ecc training are highly dependent on the muscle action usedfor training and testing. Muscle hypertrophy and neural adaptationscontribute to strength increases consequent to both Con and Ecctraining.

     

More tetanic contractions are required for activating glucose transport maximally in trained muscle

Kawanaka, Kentaro, Izumi Tabata, and MitsuruHiguchi. More tetanic contractions are requiredfor activating glucose transport maximally in trained muscle.J. Appl. Physiol. 83(2): 429-433, 1997.Exercise training increases contraction-stimulated maximalglucose transport and muscle glycogen level in skeletal muscle.However, there is a possibility that more muscle contractions arerequired to maximally activate glucose transport in trained than inuntrained muscle, because increased glycogen level after training mayinhibit glucose transport. Therefore, the purpose of this study was toinvestigate the relationship between the increase in glucose transportand the number of tetanic contractions in trained and untrained muscle.Male rats swam 2 h/day for 15 days. In untrained epitrochlearis muscle,resting glycogen was 26.6 µmol glucose/g muscle. Ten, 10-s-longtetani at a rate of 1 contraction/min decreased glycogen level to 15.4 µmol glucose/g muscle and maximally increased2-deoxy-D-glucose(2-DG) transport. Training increasedcontraction-stimulated maximal 2-DG transport (+71%;P < 0.01), GLUT-4 protein content(+78%; P < 0.01), and restingglycogen level (to 39.3 µmol glucose/g muscle;P < 0.01) on the next day after thetraining ended, although this training effect might be due, at least inpart, to last bout of exercise. In trained muscle, 20 tetani werenecessary to maximally activate glucose transport. Twenty tetanidecreased muscle glycogen to a lower level than 10 tetani (18.9 vs.24.0 µmol glucose/g muscle; P < 0.01). Contraction-stimulated 2-DG transport was negatively correlatedwith postcontraction muscle glycogen level in trained (r = 0.60;P < 0.01) and untrained muscle(r = 0.57;P < 0.01).

     

Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension

Brilli, Richard J., Brian Krafte-Jacobs, Daniel J. Smith,Dominick Roselle, Daniel Passerini, Amos Vromen, Lori Moore, CsabaSzabó, and Andrew L. Salzman. Intratracheal instillation ofa novel NO/nucleophile adduct selectively reduces pulmonary hypertension. J. Appl. Physiol. 83(6):1968-1975, 1997.We examined the pulmonary and systemichemodynamic effects of administering soluble nitric oxide (NO) donorcompounds (NO/nucleophile adducts, i.e., NONOates) directly into thetrachea of animals with experimentally induced pulmonary hypertension.Steady-state pulmonary hypertension was created by using thethromboxane agonist U-46619. Yorkshire pigs were randomly assigned toone of four groups: group 1,intratracheal saline (control; n = 8);group 2, intratracheal sodiumnitroprusside (n = 6);group 3, intratracheal ethylputreanineNONOate (n = 6); andgroup 4, intratracheal2-(dimethylamino)-ethylputreanine NONOate (DMAEP/NO;n = 6). Pulmonary and systemichemodynamics were monitored after drug instillation.Group 4 had significant reductions in pulmonary vascular resistance index (PVRI) at all time points comparedwith steady state and compared with group1 (P < 0.05), whereas systemic vascular resistance index did not change. The meanchange in mean pulmonary arterial pressure in group4 was 33.1 ± 1.2% compared with +6.4 ± 1.3% in group 1 (P < 0.001), and the mean change inmean arterial pressure was 9.3 ± 0.7% compared with acontrol value of 0.9 ± 0.5%(P < 0.05). Groups 2 and 3 hadsignificant decreases in both PVRI and systemic vascular resistanceindex compared with steady state and with group1. In conclusion, intratracheal instillation of apolar-charged tertiary amine NONOate DMAEP/NO results in the selectivereduction of PVRI. Intermittent intratracheal instillation of selectiveNONOates may be an alternative to continuously inhaled NO in thetreatment of pulmonary hypertension.

     

Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle

Bigard, Xavier A., Chantal Janmot, Danièle Merino,Françoise Lienhard, Yannick C. Guezennec, and Anne D'Albis.Endurance training affects myosin heavy chain phenotype inregenerating fast-twitch muscle. J. Appl.Physiol. 81(6): 2658-2665, 1996.The aim of thisstudy was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosinheavy chain (MHC) isoforms during and after regeneration of afast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary(n = 10) or an endurance-trained (ET;n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snaketoxin. Five days after induction of muscle injury, animals were trainedover a 5-wk period. It was verified that ~40 days after venomtreatment, central nuclei were present in the treated EDL muscles fromsedentary and ET rats. The changes in the expression of MHCs in EDLmuscles were detected by using a combination of biochemical andimmunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, andIIx MHC isoforms in ET rats were greater in regenerated EDL muscles(146%, P < 0.05; 76%,P < 0.01; 87%,P < 0.01, respectively). Their elevation corresponded to a decreasein the relative concentration of type IIb MHC (36%,P < 0.01). Although type I accountedfor only 3.2% of total myosin in regenerated muscles from the ETgroup, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.

     

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.

     

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

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

     

Effects of vigorous exercise training and beta -agonist administration on bone response to hindlimb suspension

Bloomfield, Susan A., Beverly E. Girten, and Steven E. Weisbrode. Effects of vigorous exercise training and -agonist administration on bone response to hindlimb suspension.J. Appl. Physiol. 83(1):172-178, 1997.The effectiveness of dobutamine (Dob) inpreventing bone loss during 14 days of hindlimb suspension (Sus) wastested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats(age 155 days). One-half of each group was given Dob (2 mg · kg¹ · day¹)or saline (Sal). Histomorphometric measurements at midfemur revealed a17% smaller cortical bone area (CBA) and a 32% lower periostealmineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Salrats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similarbut nonsignificant effects on cross-sectional moment of inertia wereobserved. Nonsuspended Ex rats had no change in bone CBA when CBA isindexed to body weight. Sus appeared to uncouple the relationshipbetween soleus weight and CBA. Dob attenuated the 43% decline insoleus weight after Sus in Ex but not in Sed rats. In summary, vigorousEx before Sus does not affect loss of bone mass due to unloading; Dobeffectively maintains CBA in Sed rats subjected to suspension.