Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex

Ray, Chester A., and Keith M. Hume. Neck afferents andmuscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl.Physiol. 84(2): 450-453, 1998.We have shownpreviously that head-down neck flexion (HDNF) in humans elicitsincreases in muscle sympathetic nerve activity (MSNA). The purpose ofthis study was to determine the effect of neck muscle afferents onMSNA. We studied this question by measuring MSNA before and after headrotation that would activate neck muscle afferents but not thevestibular system (i.e., no stimulation of the otolith organs orsemicircular canals). After a 3-min baseline period with the head inthe normal erect position, subjects rotated their head to the side(~90°) and maintained this position for 3 min. Head rotation wasperformed by the subjects in both the prone(n = 5) and sitting(n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed asburst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baselineand head rotation, respectively. There were no significant changes incalf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml · 100 ml¹ · min¹;n = 8) and calf vascular resistance(39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min;P = 0.058) and mean arterial pressure(90 ± 3 to 93 ± 3; P < 0.05)increased slightly during head rotation. Additional neck flexionstudies were performed with subjects lying on their side(n = 5). MSNA, heart rate, and meanarterial pressure were unchanged during this maneuver, which also doesnot engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% (P < 0.001) during HDNF. Thesefindings indicate that neck afferents activated by horizontal neckrotation or flexion in the absence of significant force development donot elicit changes in MSNA. These findings support the concept thatHDNF increases MSNA by the activation of the vestibular system.

     

Interaction between vestibulosympathetic and skeletal muscle reflexes on sympathetic activity in humans

Evidence from animalsindicates that skeletal muscle afferents activate the vestibular nucleiand that both vestibular and skeletal muscle afferents have inputs tothe ventrolateral medulla. The purpose of the present study was toinvestigate the interaction between the vestibulosympathetic andskeletal muscle reflexes on muscle sympathetic nerve activity (MSNA)and arterial pressure in humans. MSNA, arterial pressure, and heartrate were measured in 17 healthy subjects in the prone position duringthree experimental trials. The three trials were 2 min of 1)head-down rotation (HDR) to engage the vestibulosympathetic reflex,2) isometric handgrip (IHG) at 30% maximal voluntarycontraction to activate skeletal muscle afferents, and 3)HDR and IHG performed simultaneously. The order of the three trials wasrandomized. HDR and IHG performed alone increased total MSNA by 46 ± 16 and 77 ± 24 units, respectively (P < 0.01). During the HDR plus IHG trial, MSNA increased 142 ± 38 units (P < 0.01). This increase was not significantlydifferent from the sum of the individual trials (130 ± 41 units).This finding was also observed with mean arterial pressure (sum = 21 ± 2 mmHg and HDR + IHG = 22 ± 2 mmHg). Thesefindings suggest that there is an additive interaction for MSNA andarterial pressure when the vestibulosympathetic and skeletal musclereflexes are engaged simultaneously in humans. Therefore, no centralmodulation exists between these two reflexes with regard to MSNA outputin humans.

     

Sympathetic discharge and vascular resistance after bed rest

Shoemaker, J. Kevin, Cynthia S. Hogeman, Urs A. Leuenberger,Michael D. Herr, Kristen Gray, David H. Silber, and Lawrence I. Sinoway. Sympathetic discharge and vascular resistance after bedrest. J. Appl. Physiol. 84(2):612-617, 1998.The effect of 6° head-down-tilt bedrest (HDBR) for 14 days on supine sympathetic discharge andcardiovascular hemodynamics at rest was assessed. Mean arterialpressure, heart rate (n = 25), musclesympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow(n = 14) were measured, and forearmvascular resistance (FVR) was calculated. Stroke distance,our index of stroke volume, was derived from measurements of aorticmean blood velocity (Doppler) and R-R interval(n = 7). With these data, an index oftotal peripheral resistance was determined. Heart rate at rest wasgreater in the post (71 ± 2 beats/min)- compared with the pre-HDBRtest (66 ± 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic strokedistance during post-HDBR (15.5 ± 1.1 cm/beat) was reduced frompre-HDBR levels (20.0 ± 1.5 cm/beat)(P < 0.03). Also, MSNA burstfrequency was reduced in the post (16.7 ± 2.8 beats/min)- comparedwith the pre (25.2 ± 2.6 beats/min)-HDBR condition(P < 0.01). Bed rest did not alterforearm blood flow, FVR, or total peripheral resistance. Thusreductions in MSNA with HDBR were not associated with a decrease inFVR.

     

Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis

Ball, Karen T., Tania R. Gunn, Peter D. Gluckman, and GordonG. Power. Suppressive action of endogenous adenosine on ovinefetal nonshivering thermogenesis. J. Appl.Physiol. 81(6): 2393-2398, 1996.Nonshiveringthermogenesis is not initiated when the fetal sheep is cooled in uterobut appears to require the removal of an inhibitor of placental originat birth. To test whether adenosine is such an inhibitor, we examinedthe effect of the adenosine antagonist theophylline on the initiationof nonshivering thermogenesis during sequential cooling, ventilation, and umbilical cord occlusion in utero. Theophylline (18 mg/kg bolus and0.6 mg ^· kg^{1 ·} min¹thereafter) was infused for 90 min before and 90 min after cord occlusion. Theophylline enhanced the nonshivering thermogenic freefatty acid (FFA) and glycerol responses before cord occlusion, raisingFFA concentrations 99% to 415 ± 60 µeq/l(P < 0.01) and glycerol levels 87%to 526 ± 135 µmol/l (P < 0.05). These FFA (P < 0.001) andglycerol (P < 0.05) concentrationswere significantly greater than the corresponding period during thebirth-simulation control. Umbilical cord occlusion did not alter FFAlevels but induced a 41% rise in glycerol concentrations to 774 ± 203 µmol/l (P < 0.05). Theincreases in nonshivering thermogenic indexes after the administrationof the adenosine-receptor antagonist suggest that the quiescent stateof ovine fetal brown adipose tissue may result, in part, from the tonicinhibitory actions of adenosine and that a decrease in adenosineconcentrations enhances nonshivering thermogenesis. However, thefurther rise after umbilical cord occlusion suggests that at least oneother inhibitor of placental origin inhibits nonshivering thermogenesisbefore birth.

     

Augmentation of exercise-induced muscle sympathetic nerve activity during muscle heating

Ray, Chester A., and Kathryn H. Gracey. Augmentation ofexercise-induced muscle sympathetic nerve activity during muscle heating. J. Appl. Physiol. 82(6):1719-1725, 1997.The muscle metabo- and mechanoreflexes have beenshown to increase muscle sympathetic nerve activity (MSNA) duringexercise. Group III and IV muscle afferents, which are believed tomediate this response, have been shown to be thermosensitive inanimals. The purpose of the present study was to evaluate the effect ofmuscle temperature on MSNA responses during exercise. Eleven subjectsperformed ischemic isometric handgrip at 30% of maximal voluntarycontraction to fatigue, followed by 2 min of postexercise muscleischemia (PEMI), with and without local heating of the forearm. Localheating of the forearm increased forearm muscle temperature from 34.4 ± 0.2 to 38.9 ± 0.3°C(P = 0.001). Diastolic andmean arterial pressures were augmented during exercise in the heat.MSNA responses were greater during ischemic handgrip with local heatingcompared with control (no heating) after the first 30 s. MSNA responsesat fatigue were greater during local heating. MSNA increased by 16 ± 2 and 20 ± 2 bursts per 30 s for control and heating,respectively (P = 0.03). Whenexpressed as a percent change in total activity (total burstamplitude), MSNA increased 531 ± 159 and 941 ± 237% forcontrol and heating, respectively (P = 0.001). However, MSNA was not different during PEMI between trials.This finding suggests that the augmentation of MSNA during exercisewith heat was due to the stimulation of mechanically sensitive muscleafferents. These results suggest that heat sensitizes skeletal muscleafferents during muscle contraction in humans and may play a role inthe regulation of MSNA during exercise.

     

Microdialysis ethanol removal reflects probe recovery rather than local blood flow in skeletal muscle

The present study compared the microdialysis ethanoloutflow-inflow technique for estimating blood flow (BF) in skeletalmuscle of humans with measurements by Doppler ultrasound of femoralartery inflow to the limb(BF_FA). The microdialysis probeswere inserted in the vastus lateralis muscle and perfused with a Ringeracetate solution containing ethanol,[2-³H]adenosine (Ado),andD-[¹⁴C(U)]glucose.BF_FA at rest increased from0.16 ± 0.02 to 1.80 ± 0.26 and 4.86 ± 0.53 l/minwith femoral artery infusion of Ado (Ado_FA,i) at 125 and 1,000 µg · min¹ · l¹thigh volume (low dose and high dose, respectively;P < 0.05) and to 3.79 ± 0.37 and6.13 ± 0.65 l/min during one-legged, dynamic, thigh muscle exercisewithout and with high Ado_FA,i,respectively (P < 0.05). The ethanoloutflow-to-inflow ratio (38.3 ± 2.3%) and the probe recoveries(PR) for [2-³H]Ado(35.4 ± 1.6%) and forD-[¹⁴C(U)]glucose(15.9 ± 1.1%) did not change withAdo_FA,i at rest (P = not significant). During exercisewithout and with Ado_FA,i, theethanol outflow-to-inflow ratio decreased(P < 0.05) to a similar level of17.5 ± 3.4 and 20.6 ± 3.2%, respectively(P = not significant), respectively,while the PR increased (P < 0.05) toa similar level (P = not significant)of 55.8 ± 2.8 and 61.2 ± 2.5% for[2-³H]Ado and to 42.8 ± 3.9 and 45.2 ± 5.1% forD-[¹⁴C(U)]glucose.Whereas the ethanol outflow-to-inflow ratio and PR correlated inverselyand positively, respectively, to the changes in BF during muscularcontractions, neither of the ratio nor PR correlated tothe Ado_FA,i-induced BF increase.Thus the ethanol outflow-to-inflow ratio does not represent skeletalmuscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.

     

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat

We used the microdialysis technique to measurethe interstitial concentration of several putative metabolic stimulantsof the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 ± 5 beats/min and 21 ± 8 mmHg and 27 ± 9 beats/min and 37 ± 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned tobaseline after 10 min of recovery. Interstitial lactate rose (P < 0.05) by 0.41 ± 0.15 and0.56 ± 0.16 mM for the 3- and 5-Hz stimulation protocols,respectively, and were not statistically different from one another.Interstitial lactate levels remained above(P < 0.05) baseline during recoveryin the 5-Hz group. Dialysate phosphate concentrations (corrected forshifts in probe recovery) rose with stimulation(P < 0.05) by 0.19 ± 0.08 and0.11 ± 0.03 mM for the 3- and 5-Hz protocols. There were nodifferences between groups. The resting dialysateK⁺ concentrations for the 3- and5-Hz conditions were 4.0 ± 0.1 and 3.9 ± 0.1 meq/l,respectively. During stimulation the dialysate K⁺ concentrations rose steadilyfor both conditions, and the increase from rest to stimulation(P < 0.05) was 0.57 ± 0.19 and0.81 ± 0.06 meq/l for the 3- and 5-Hz conditions, respectively,with no differences between groups. Resting dialysate pH was6.915 ± 0.055 and 6.981 ± 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hzconditions, respectively, and then became acidotic (6.905, P < 0.05) during recovery (5 Hzonly). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These datasuggest that interstitial K⁺ andphosphate, but not lactate and H⁺,may contribute to the stimulation of thin fiber muscle afferents duringcontraction.

     

Effect of concentric and eccentric muscle actions on muscle sympathetic nerve activity

The purpose ofthis study was to determine the effects of concentric (Con) andeccentric (Ecc) muscle actions on leg muscle sympathetic nerve activity(MSNA). Two protocols were utilized. In protocol1, eight subjects performed Con and Ecc arm curls for 2 min, with a resistance representing 50% of one-repetition maximum forCon curls. Heart rate (HR) and mean arterial pressure (MAP) weregreater (P < 0.05) during Con thanduring Ecc curls. Similarly, the MSNA was greater(P < 0.05) during Con than during Ecc curls. In protocol 2, eightdifferent subjects performed Con and Ecc arm curls to fatigue, followedby postexercise muscle ischemia, by using the same resistanceas in protocol 1. Endurance time wassignificantly greater for Ecc than for Con curls. The increase in HR,MAP, and MSNA was greater (P < 0.05)during Con than during Ecc curls. However, when the data werenormalized as a function of endurance time, the differences in HR, MAP,and MSNA between Con and Ecc curls were no longer present. HR, MAP, andMSNA responses during postexercise muscle ischemia were similar for Con and Ecc curls. Con curls elicited greater increase(P < 0.05) in blood lactateconcentration than did Ecc curls. In summary, Con actions contributesignificantly more to the increase in cardiovascular and MSNA responsesduring brief, submaximal exercise than do Ecc actions. However, whenperformed to a similar level of effort (i.e., fatigue), Con and Eccmuscle actions elicit similar cardiovascular and MSNA responses. Theseresults indicate that the increase in MSNA during a typical bout ofsubmaximal dynamic exercise is primarily mediated by the musclemetaboreflex, which is stimulated by metabolites produced predominantlyduring Con muscle action.     

Contribution of abdomen and legs to central blood volume expansion in humans during immersion

Johansen, Lars Bo, Thomas Ulrik Skram Jensen, Bettina Pump,and Peter Norsk. Contribution of abdomen and legs to central bloodvolume expansion in humans during immersion. J. Appl.Physiol. 83(3): 695-699, 1997.The hypothesis wastested that the abdominal area constitutes an important reservoir forcentral blood volume expansion (CBVE) during water immersion inhumans. Six men underwent 1) water immersion for 30 min (WI),2) water immersion for 30 min withthigh cuff inflation (250 mmHg) during initial 15 min to exclude legsfrom contributing to CBVE (WI+Occl), and3) a seated nonimmersed control with15 min of thigh cuff inflation (Occl). Plasma protein concentration andhematocrit decreased from 68 ± 1 to 64 ± 1 g/l and from 46.7 ± 0.3 to 45.5 ± 0.4%(P < 0.05), respectively, during WIbut were unchanged during WI+Occl. Left atrial diameter increased from27 ± 2 to 36 ± 1 mm (P < 0.05) during WI and increased similarly during WI+Occl from 27 ± 2 to 35 ± 1 mm (P < 0.05). Centralvenous pressure increased from 3.7 ± 1.0 to 10.4 ± 0.8 mmHg during WI (P < 0.05) butonly increased to 7.0 ± 0.8 mmHg during WI+Occl(P < 0.05). In conclusion, the dilution of blood induced by WI to the neck is caused by fluid from thelegs, whereas the CBVE is caused mainly by blood from theabdomen.

     

Comparative hemodynamic effects of periodic obstructive and simulated central apneas in sedated pigs

Chen, Ling, and Steven M. Scharf. Comparativehemodynamic effects of periodic obstructive and simulated centralapneas in sedated pigs. J. Appl.Physiol. 83(2): 485-494, 1997.It has beenspeculated that because of increased left ventricular (LV) afterload,decreased intrathoracic pressure (ITP) is responsible for decreasedcardiac output (CO) in obstructive sleep apnea. If this were true, thenobstructive apnea (OA) should have a greater effect on CO than wouldcentral apnea (CA). To assess the importance of decreasedITP during OA, we studied seven preinstrumented sedated pigs with OAand simulated CA that were matched for blood gases and apneaperiodicities (with 15- or 30-s apnea duration). Compared with OA, CAwith 30-s apnea duration produced comparable decreases in heart rate(from baseline to end apnea: OA, 106.6 ± 4.8 to 93.4 ± 4.4 beats/min, P < 0.01; and CA, 111.1 ± 6.2 to 94.0 ± 5.2 beats/min,P < 0.01) and comparable increasesin LV end-diastolic pressure and LV end-diastolic myocardial segmentlength but greater increases in mean arterial pressure (97.1 ± 3.7 to 107.7 ± 4.3 Torr, P < 0.05;and 97.3 ± 4.8 to 119.3 ± 7.4 Torr,P < 0.01) and systemic vascularresistance (2,577 ± 224 to 3,346 ± 400 dyn · s · cm⁵,P < 0.01; and 2,738 ± 294 to5,111 ± 1,181 dyn · s · cm⁵,P < 0.01) and greater decreases inCO (3.18 ± 0.31 to 2.74 ± 0.26 l/min,P < 0.05; and 3.07 ± 0.38 to2.30 ± 0.36 l/min, P < 0.01) andstroke volume (32.2 ± 2.9 to 25.9 ± 2.4 ml,P < 0.05; and 31.5 ± 1.9 to 19.8 ± 3.1 ml, P < 0.01). Only CA increased LV end-systolic myocardialsegment length. Similar findings were observed with 15-s apneaduration. We conclude that CA produced greater depression of CO andgreater changes of afterload-related LV dysfunction than did OA.Therefore, decreased ITP was not the dominant factor determining LVfunction with apneas.

     

Tissue factor activity is increased in human endothelial cells cultured under elevated static pressure

We tested the hypothesis that elevated blood pressure, a knownstimulus for vascular remodeling and an independent risk factor for thedevelopment of atherosclerotic disease, can modulate basal andcytokine-induced tissue factor (TF; CD 142) expression in culturedhuman endothelial cells (EC). Using a chromogenic enzymatic assay, wemeasured basal and tumor necrosis factor- (TNF-; 10 ng/ml, 5 h)-induced TF activities in human aortic EC (HAEC) and vena cava EC(HVCEC) cultured at atmospheric pressure and at 170 mmHg imposedpressure for up to 48 h. Basal TF activities were 22 ± 10 U/mgprotein for HAEC and 14 ± 9 U/mg protein for HVCEC and wereupregulated in both cell types >10-fold by TNF-. Exposure topressure for 5 h induced additional elevation of basal TF activity by47 ± 16% (P < 0.05, n = 6) for HAEC and 17 ± 5%(P < 0.05, n = 3) for HVCEC. Pressurization alsoenhanced TF activity in TNF--treated cells from 240 ± 28 to 319 ± 32 U/mg protein in HAEC (P < 0.05, n = 4) and from 148 ± 25 to179 ± 0.8 U/mg protein (P < 0.05, n = 3) in HVCEC. Cytokinestimulation caused an ~100-fold increase in steady-state TF mRNAlevels in HAEC, whereas pressurization did not alter either TF mRNA orcell surface antigen expression, as determined by quantitative RT-PCRmethodology and ELISA. Elevated pressure, however, modulated the ECplasma membrane organization and/or permeability as inferred from theincreased cellular uptake of the fluorescent amphipathic dyemerocyanine 540 (33 ± 7%, P < 0.05). Our data suggest that elevated static pressure modulates thehemostatic potential of vascular cells by modifying the molecular organization of the plasma membrane.

     

Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs

Ventilation during ischemia attenuatesischemia-reperfusion lung injury, but the mechanism is unknown.Increasing tissue cyclic nucleotide levels has been shown to attenuatelung ischemia-reperfusion injury. We hypothesized thatventilation prevented increased pulmonary vascular permeability duringischemia by increasing lung cyclic nucleotide concentrations.To test this hypothesis, we measured vascular permeability and cGMP andcAMP concentrations in ischemic (75 min) sheep lungs that wereventilated (12 ml/kg tidal volume) or statically inflated with the samepositive end-expiratory pressure (5 Torr). The reflection coefficientfor albumin (_alb) was 0.54 ± 0.07 and 0.74 ± 0.02 (SE) in nonventilated and ventilatedlungs, respectively (n = 5, P < 0.05). Filtration coefficientsand capillary blood gas tensions were not different. The effect ofventilation was not mediated by cyclic compression of alveolarcapillaries, because negative-pressure ventilation(n = 4) also was protective (_alb = 0.78 ± 0.09). Thefinal cGMP concentration was less in nonventilated than in ventilatedlungs (0.02 ± 0.02 and 0.49 ± 0.18 nmol/g blood-free dry wt,respectively, n = 5, P < 0.05). cAMP concentrations werenot different between groups or over time. Sodium nitroprussideincreased cGMP (1.97 ± 0.35 nmol/g blood-free dry wt) and_alb (0.81 ± 0.09) innonventilated lungs (n = 5, P < 0.05). Isoproterenol increasedcAMP in nonventilated lungs (n = 4, P < 0.05) but had no effect on_alb. The nitric oxide synthaseinhibitor N^G-nitro-L-arginine methylester had no effect on lung cGMP (n = 9) or _alb(n = 16) in ventilated lungs but didincrease pulmonary vascular resistance threefold(P < 0.05) in perfused sheep lungs (n = 3). These results suggest thatventilation during ischemia prevented an increase in pulmonaryvascular protein permeability, possibly through maintenance of lungcGMP by a nitric oxide-independent mechanism.

     

Effects of the ovarian cycle on sympathetic neural outflow during static exercise

We comparedreflex responses to static handgrip at 30% maximal voluntarycontraction (MVC) in 10 women (mean age 24.1 ± 1.7 yr) during twophases of their ovarian cycle: the menstrual phase (days 1-4) and the follicularphase (days10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response tostatic exercise were greater during the menstrual compared withfollicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase(75 ± 5.5 vs. 116 ± 9.6 pg/ml, days 1-4 vs.days 10-12;P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 ± 1.3 vs. 28.2 ± 1.5 kg, days 1-4 vs.days 10-12;P = 0.13). In a group of experiments with the use of ³¹P-NMRspectroscopy, no phase effect was observed forH⁺ andH₂PO₄ concentrations(n = 5). During an ischemicrhythmic handgrip paradigm (20% MVC), a phase effect was notobserved for MSNA or H⁺ orH₂PO₄ concentrations,suggesting that blood flow was necessary for the expression of thecycle-related effect. The present studies suggest that, during statichandgrip exercise, MSNA is increased during the menstrual compared withthe follicular phase of the ovarian cycle.

     

Prostaglandin production contributes to exercise-induced vasodilation in heart failure

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor,and John R. Wilson. Prostaglandin production contributes toexercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933-1940, 1997.Endothelial release of prostaglandins may contribute toexercise-induced skeletal muscle arteriolar vasodilation in patientswith heart failure. To test this hypothesis, we examined the effect ofindomethacin on leg circulation and metabolism in eight chronic heartfailure patients, aged 55 ± 4 yr. Central hemodynamics and legblood flow, determined by thermodilution, and leg metabolic parameterswere measured during maximum treadmill exercise before and 2 h afteroral administration of indomethacin (75 mg). Leg release of6-ketoprostaglandin F₁ was alsomeasured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min(P < 0.001), legO₂ consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to267.4 ± 35.8 pg/min (P < 0.001).Indomethacin suppressed release of prostaglandinF₁(P < 0.001) throughout exercise anddecreased leg blood flow during exercise(P < 0.05). This was associated witha corresponding decrease in leg O₂ consumption (P < 0.05) and a higher level offemoral venous lactate at peak exercise(P < 0.01). These data suggest thatrelease of vasodilatory prostaglandins contributes to skeletal musclearteriolar vasodilation in patients with heart failure.

     

Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats

Brainnatriuretic peptide (BNP) is a pulmonary vasodilator that is elevatedin the right heart and plasma of hypoxia-adapted rats. To test thehypothesis that BNP protects against hypoxic pulmonary hypertension, wemeasured right ventricular systolic pressure (RVSP), right ventricle(RV) weight-to-body weight (BW) ratio (RV/BW), and percentmuscularization of peripheral pulmonary vessels (%MPPV) in rats givenan intravenous infusion of BNP, atrial natriuretic peptide (ANP), orsaline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm).Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPVthan did normoxic controls. Under normoxic conditions, BNP infusion(0.2 and 1.4 µg/h) increased plasma BNP but had no effect on RVSP,RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 µg/h) had no effect on plasma BNP or on severity of pulmonaryhypertension. However, high-rate BNP infusion (1.4 µg/h) increasedplasma BNP (69 ± 8 vs. 35 ± 4 pg/ml, P < 0.05),lowered RV/BW (0.87 ± 0.05 vs. 1.02 ± 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%,P < 0.05). There was also a trend towardlower RVSP (55 ± 3 vs. 64 ± 2, P = not significant).Infusion of ANP at 1.4 µg/h increased plasma ANP in hypoxic rats (759 ± 153 vs. 393 ± 54 pg/ml, P < 0.05) but had noeffect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulatepulmonary vascular responses to hypoxia and, at the doses used in thisstudy, is more effective than ANP at blunting pulmonary hypertensionduring the first 2 wk of hypoxia.

     

Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit

Campbell, Hillary, Krishnan Ravi, Emigdio Bravo, and C. Tissa Kappagoda. Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit. J. Appl.Physiol. 81(6): 2604-2610, 1996.The effects ofDiazinon PLUS aerosol on the activities of rapidly adapting receptors(RARs) and slowly adapting receptors (SAR) of the airways wereinvestigated in anesthetized rabbits. The effects on boththe baseline activity and the responses to stimulation by increasingmean left atrial pressure were examined. Action potentialswere recorded from the left cervical vagus nerve. Aerosols (particlesize 3 µm) were generated by a Mini-HEART nebulizer. We observed thatan aerosol of Diazinon PLUS (1:10 vol/vol dilution in normal saline)decreased the baseline RAR activity (n = 10) significantly (P < 0.05) from209 ± 77 to 120 ± 40 impulses/min. In the post-Diazinon PLUScontrol period, the RAR activity recovered partially to 185 ± 75 impulses/min and decreased significantly to 131 ± 52 impulses/min(P < 0.05) after a second exposureof Diazinon PLUS (undiluted) aerosol. Aerosols of normal saline in thecontrol state did not produce a significant change in the RAR activity.A group of SAR (n = 8) were examinedunder similar conditions, and it was found that only the exposure toDiazinon PLUS (undiluted) aerosol decreased the activity significantly (P < 0.05) from 1,536 ± 206 to1,367 ± 182 impulses/min. The effect of Diazinon PLUS on theresponse to increasing mean left atrial pressure was examined in sevenRARs. In the control state, RAR activity increased significantly(P < 0.05) during elevation of meanleft atrial pressure. This response was abolished after exposure toDiazinon PLUS. These findings suggest that diazinon may interfere withairway defense mechanisms by reducing the activity of RARs.

     

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure

To elucidate thetime course of sympathovagal balance and its relationship to leftventricular function in heart failure, we serially evaluated leftventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined adynamic map of sympathetic and parasympathetic modulation by powerspectral analysis of heart rate variability. The left ventricular peak+dP/dt substantially fell from 3,364 ± 338 to 1,959 ± 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 ± 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the timeconstant of left ventricular pressure decay and end-diastolic pressureincreased gradually from 25 ± 4 to 47 ± 5 ms(P < 0.05) and from 10 ± 2 to21 ± 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component(0.15-1.0 Hz), a marker of parasympathetic modulation, decreasedfrom 1,928 ± 1,914 to 62 ± 68 × 10³ms²(P < 0.05) on the third day andfurther to 9 ± 12 × 10³ms²(P < 0.05) at 2 wk. Similar to thetime course of left ventricular diastolic dysfunction, plasmanorepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- tohigh-frequency component increased progressively from 135 ± 50 to 532 ± 186 pg/ml (P < 0.05) and from 0.06 ± 0.06 to 1.12 ± 1.01 (P < 0.05), respectively, at 2 wk ofpacing. These cardiac and autonomic dysfunctions recovered graduallytoward the normal values at 2 wk after cessation of pacing. Thus aparallel decline in left ventricular contractility with parasympatheticinfluence and a parallel progression in left ventricular diastolicdysfunction with sympathoexcitation suggest a close relationshipbetween cardiac dysfunction and autonomic dysregulation duringdevelopment of heart failure.

     

Reflex responses to regional venous pooling during lower body negative pressure in humans

Halliwill, John R., Lori A. Lawler, Tamara J. Eickhoff,Michael J. Joyner, and Sharon L. Mulvagh. Reflex responses toregional venous pooling during lower body negative pressure in humans.J. Appl. Physiol. 84(2): 454-458, 1998.Lower body negative pressure is frequently used to simulateorthostasis. Prior data suggest that venous pooling in abdominal orpelvic regions may have major hemodynamic consequences. Therefore, we developed a simple paradigm for assessing regional contributions tovenous pooling during lower body negative pressure. Sixteen healthy menand women underwent graded lower body negative pressure protocols to 60 mmHg while wearing medical antishock trousers to prevent venous poolingunder three randomized conditions:1) no trouser inflation (control),2) only the trouser legs inflated, and 3) the trouser legs andabdominopelvic region inflated. Without trouser inflation, heart rateincreased 28 ± 4 beats/min, mean arterial pressure fell 3 ± 2 mmHg, and forearm vascular resistance increased 51 ± 9 units at 60 mmHg lower body negative pressure. With inflation of eitherthe trouser legs or the trouser legs and abdominopelvic region, heartrate and mean arterial pressure did not change during lower bodynegative pressure. By contrast, although the forearm vasoconstrictorresponse to lower body negative pressure was attenuated by inflation ofthe trouser legs (forearm vascular resistance 33 ± 10 units,P < 0.05 vs. control), attenuation was greater with the inflation of the trouser legs and abdominopelvic region (forearm vascular resistance 16 ± 5 units,P < 0.05 vs. control and trouserlegs-only inflation). Thus the hemodynamic consequences of pooling inthe abdominal and pelvic regions during lower body negative pressureappear to be less than in the legs in healthy individuals.

     

Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep

Rapid eyemovements during rapid-eye-movement (REM) sleep are associated withrapid, shallow breathing. We wanted to know whether thiseffect persisted during increased respiratory drive byCO₂. In eight healthy subjects, werecorded electroencephalographic, electrooculographic, andelectromyographic signals, ventilation, and end-tidalPCO₂ during the night. InspiratoryPCO₂ was changed to increaseend-tidal PCO₂ by 3 and 6 Torr. During normocapnia, rapid eye movements were associated with a decreasein total breath time by 0.71 ± 0.19 (SE) s(P < 0.05) because of shortenedexpiratory time (0.52 ± 0.08 s,P < 0.001) and with a reduced tidalvolume (89 ± 27 ml, P < 0.05) because of decreased rib cage contribution (75 ± 18 ml, P < 0.05). Abdominal (11 ± 16 ml, P = 0.52) and minuteventilation (0.09 ± 0.21 ml/min, P = 0.66) did not change. Inhypercapnia, however, rapid eye movements were associated with afurther shortening of total breath time. Abdominal breathing was alsoinhibited (79 ± 23 ml, P < 0.05), leading to a stronger inhibition of tidal volume and minuteventilation (1.84 ± 0.54 l/min,P < 0.05). We conclude thatREM-associated respiratory changes are even more pronounced duringhypercapnia because of additional inhibition of abdominal breathing.This may contribute to the reduction of the hypercapnic ventilatory response during REM sleep.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.