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.

     

Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses

To test thehypothesis that head-down-tilt bed rest (HDBR) for 14 days altersvascular reactivity to vasodilatory and vasoconstrictor stimuli, thereactive hyperemic forearm blood flow (RHBF, measured by venousocclusion plethysmography) and mean arterial pressure (MAP, measured byFinapres) responses after 10 min of circulatory arrest were measured ina control trial (n = 20) and whensympathetic discharge was increased by a cold pressor test (RHBF + coldpressor test; n = 10). Vascularconductance (VC) was calculated (VC = RHBF/MAP). In the control trial,peak RHBF at 5 s after circulatory arrest (34.1 ± 2.5 vs.48.9 ± 4.3 ml · 100 ml¹ · min¹)and VC (0.34 ± 0.02 vs. 0.53 ± 0.05 ml · 100 ml¹ · min¹ · mmHg¹)were reduced in the post- compared with the pre-HDBR tests(P < 0.05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). Theability of the cold pressor test to lower forearm blood flow was lessin the post- than in the pre-HDBR test(P < 0.05), despite similarincreases in MAP. These data suggest that regulation of vasculardilation and the interaction between dilatory and constrictorinfluences were altered with bed rest.

     

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.

     

Sympathetic withdrawal and forearm vasodilation during vasovagal syncope in humans

Dietz, Niki M., John R. Halliwill, John M. Spielmann, LoriA. Lawler, Bettina G. Papouchado, Tamara J. Eickhoff, and Michael J. Joyner. Sympathetic withdrawal and forearm vasodilation duringvasovagal syncope in humans. J. Appl.Physiol. 82(6): 1785-1793, 1997.Our aim was todetermine whether sympathetic withdrawal alone can account for theprofound forearm vasodilation that occurs during syncope in humans. Wealso determined whether either vasodilating ₂-adrenergic receptors ornitric oxide (NO) contributes to this dilation. Forearm blood flow wasmeasured bilaterally in healthy volunteers(n = 10) by using plethysmographyduring two bouts of graded lower body negative pressure (LBNP) tosyncope. In one forearm, drugs were infused via a brachial arterycatheter while the other forearm served as a control. In the controlarm, forearm vascular resistance (FVR) increased from 77 ± 7 unitsat baseline to 191 ± 36 units with 40 mmHg of LBNP(P < 0.05). Mean arterial pressurefell from 94 ± 2 to 47 ± 4 mmHg just before syncope, and allsubjects demonstrated sudden bradycardia at the time of syncope. At theonset of syncope, there was sudden vasodilation and FVR fell to 26 ± 6 units (P < 0.05 vs. baseline). When the experimental forearm was treated withbretylium, phentolamine, and propranolol, baseline FVR fell to 26 ± 2 units, the vasoconstriction during LBNP was absent, and FVR fellfurther to 16 ± 1 units at syncope(P < 0.05 vs. baseline). During thesecond trial of LBNP, mean arterial pressure again fell to 47 ± 4 mmHg and bradycardia was again observed. Treatment of the experimentalforearm with the NO synthase inhibitorN^G-monomethyl-L-arginine in additionto bretylium, phentolamine, and propranolol significantly increasedbaseline FVR to 65 ± 5 units but did not prevent the marked forearmvasodilation during syncope (FVR = 24 ± 4 vs. 29 ± 8 units inthe control forearm). These data suggest that the profound vasodilationobserved in the human forearm during syncope is not mediated solely bysympathetic withdrawal and also suggest that neither₂-adrenergic-receptor-mediated vasodilation nor NO is essential to observe this response.

     

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 renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs

Smith, Francine G., Suzanne Chan, and Saskia N. De Wildt.Effects of renal denervation on cardiovascular and renal responsesto ACE inhibition in conscious lambs. J. Appl.Physiol. 83(2): 414-419, 1997.Cardiovascular andrenal effects of either the angiotensin-converting enzyme inhibitorcaptopril or vehicle were measured in chronically instrumented lambs inthe presence (intact; n = 6) andabsence of renal sympathetic nerves (denervated; n = 5) to determine whether there wasan interaction between the renin-angiotensin system and renalsympathetic nerves early in life. Captopril caused a similar decreasein mean arterial pressure (P < 0.001) in intact and denervated lambs, predominantly through a decreasein diastolic pressure. Heart rate was increased from 177 ± 34 to213 ± 22 (SD) beats/min during captopril compared with vehicleinfusion in intact lambs. In denervated lambs, basal heart rates wereelevated to 218 ± 33 beats/min; there was no further increase inheart rate during captopril compared with vehicle infusion. Captoprilinfusion caused a decrease in renal vascular resistance but only in theabsence of renal nerves. These findings provide evidence to suggestthat early in life there is an interaction between renal sympatheticnerves and the renin-angiotensin system in regulating renalhemodynamics and the baroreflex control of the heart.

     

Ocular and regional cerebral blood flow in aging Fischer-344 rats

Vascularremodeling and changes in vascular responsiveness occur in the ratcerebrum with old age. This includes reductions in cerebral arteriolarnumerical density, cross-sectional area, distensibility, the relativeproportion of distensible elements in the cerebral arteriolar wall, andreduced endothelium-dependent relaxation. The purpose of this study wasto test the hypothesis that old age results in an increase in vascularresistance and, correspondingly, a decrease in blood flow to ocular,regional cerebral, and spinal tissue in the rat. Blood flow wasmeasured in the eye, olfactory bulb, left and right cerebrum, pituitary gland, midbrain, pons, cerebellum, medulla, and spinal cord of juvenile(2-mo-old, n = 6), adult (6-mo-old,n = 7), and aged (24-mo-old,n = 7) male Fischer-344 rats. Arterialpressure and blood flow were used to calculate vascular resistance.Vascular resistance in the eye of aged rats (6.03 ± 1.08 mmHg · ml¹ · min · 100 g) was higher than that in juvenile (3.83 ± 0.38 mmHg · ml¹ · min · 100 g) and adult rats (3.12 ± 0.24 mmHg · ml¹ · min · 100 g). Similarly, resistance in the pons of older rats (2.24 ± 0.55 mmHg · ml¹ · min · 100 g) was greater than in juvenile (0.66 ± 0.06 mmHg ·ml¹ · min · 100 g) and adult rats (0.80 ± 0.11 mmHg · ml¹ · min · 100 g). In contrast, vascular resistance in the pituitary gland was lowerin the aged rats (juvenile, 3.09 ± 0.22; adult, 2.79 ± 0.42;aged, 1.73 ± 0.32 mmHg · ml¹ · min · 100 g, respectively). Vascular resistance was not different in othercerebral tissues or in the spinal cord in the aged rats. These datasuggest that regional cerebral and spinal blood flow and vascularresistance remain largely unchanged in conscious aged rats at rest butthat elevations in ocular vascular resistance and, correspondingly,decreases in ocular perfusion with advanced age could have seriousadverse effects on visual function.

     

Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus solitarii of conscious rats

This study aimedto determine the role of protein kinase C (PKC) in signal transductionmechanisms underlying ventilatory regulation in the nucleus tractussolitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate intothe commissural NTS of nine chronically instrumented, unrestrained ratselicited significant cardiorespiratory enhancements that lasted for atleast 4 h, whereas administration of vehicle(n = 15) or the inactive phorbol ester 4-phorbol 12,13-didecanoate (n = 7)did not elicit minute ventilation (E)changes. Peak hypoxic Eresponses (10% O₂-balanceN₂) were measured in 19 additional animals after NTS microinjection of bisindolylmaleimide(BIM) I, a selective PKC inhibitor (n = 12), BIM V (inactive analog; n = 7),or vehicle (Con; n = 19). In Con,E increased from 139 ± 9 to 285 ± 26 ml/min in room air and hypoxia, respectively, and similarresponses occurred after BIM V. BIM I did not affect room airE but markedly attenuated hypoxia-induced E increases (128 ± 12 to 167 ± 18 ml/min; P < 0.02 vs. Con and BIM V). When BIM I was microinjected into the cerebellum(n = 4), cortex(n = 4), or spinal cord(n = 4),E responses were similar to Con.Western blots of subcellular fractions of dorsocaudal brain stemlysates revealed translocation of PKC, , , , , and  isoenzymes during acute hypoxia, and enhanced overall PKC activity wasconfirmed in the particulate fraction of dorsocaudal brain stem lysatesharvested after acute hypoxia. These studies suggest that, in the adultrat, PKC activation in the NTS mediates essential components of theacute hypoxic ventilatory response.

     

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.

     

Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure in the isolated heart

A goal ofclinicians caring for heart transplant recipients has been to use heartrate variability as a noninvasive means of diagnosing graftrejection. The determinants of beat-to-beat variability inthe surgically denervated heart have yet to be elucidated. We used anisolated, blood buffer-perfused porcine heart preparation toquantitatively assess the relationship between coronary perfusion andsinus node automaticity. Hearts(n = 9) were suspended in aLangendorff preparation, and heart rate (HR) fluctuations werequantified while perfusion pressure was modulated between 70/50, 80/60,90/70, and 100/80 mmHg at 0.067 Hz. In 32 of 32 recordings, the crossspectrum of perfusion pressure vs. HR showed the largest peak centeredat 0.067 Hz. In eight of nine experiments during nonpulsatileperfusion, HR accelerated as perfusion pressure was increased from 40 to 110 mmHg (mean increase 24.2 ± 3.0 beats/min). HR increased 0.34 beats/min per mmHg increase in perfusion pressure (least squares linearregression y = 25.8 mmHg + 0.34x;r = 0.88, P < 0.0001). Administration of low-and high-dose nitroglycerin (Ntg) resulted in a modest increase in flowbut produced a significant decrease in HR and blunted the response ofHR to changes in perfusion pressure (HR increase 0.26 beats · min¹ · mmHg¹,r = 0.87, P < 0.0001 after low-dose Ntg; 0.25 beats · min¹ · mmHg¹,r = 0.78, P < 0.0001 after high-dose Ntg).These experiments suggest that sinus node discharge in the isolatedperfused heart is mechanically coupled to perfusion pressure on abeat-to-beat basis.     

Femoral arterial injection of adenosine in humans elevates MSNA via central but not peripheral mechanisms

MacLean, D. A., B. Saltin, G. Rådegran, and L. Sinoway. Femoral arterial injection of adenosine in humanselevates MSNA via central but not peripheral mechanisms.J. Appl. Physiol. 83(4):1045-1053, 1997.The purpose of the present study was to examinethe effects of femoral arterial injections of adenosine on musclesympathetic nerve activity (MSNA) under three different conditions.These conditions were adenosine injection alone, adenosine injectionafter phenylephrine infusion, and adenosine injection distal to a thighcuff inflated to arrest the circulation. The arterial injection ofadenosine alone resulted in a fourfold (255 ± 18 U/min) increaseabove baseline (73 ± 12 U/min; P < 0.05) in MSNA with an onset latency of 15.8 ± 0.8 s from thetime of injection. The systemic infusion of phenylephrine resulted in an increase (P < 0.05) in meanarterial pressure of ~10 mmHg and a decrease(P < 0.05) in heart rate of8-10 beats/min compared with baseline values before phenylephrineinfusion. After adenosine injection, the onset latency for the increasein MSNA was delayed to 19.2 ± 2.1 s and the magnitude of increasewas attenuated by ~50% (123 ± 20 U/min) compared with adenosineinjection alone (P < 0.05). When acuff was inflated to 220 mmHg to arrest the circulation and adenosinewas injected into the leg distal to the inflated cuff, there were nosignificant changes in MSNA or any of the other measured variables.However, on deflation of the cuff, there was a rapid increase(P < 0.05) in MSNA, with an onsetlatency of 9.1 ± 0.9 s, and the magnitude of increase (276 ± 28 U/min) was similar to that observed for adenosine alone. These datasuggest that ~50% of the effects of exogenously administered adenosine are a result of baroreceptor unloading due to a drop in bloodpressure. Furthermore, the finding that adenosine did not directlyresult in an increase in MSNA while it was trapped in the leg but thatit needed to be released into the circulation suggests that adenosinedoes not directly stimulate thin fiber muscle afferents in the leg ofhumans. In contrast, it would appear that adenosine exerts its effectsvia some other chemically sensitive pool of afferents.

     

Role of inhibition of nitric oxide production in monocrotaline-induced pulmonary hypertension

Mathew, Rajamma, Elizabeth S. Gloster, T. Sundararajan, Carl I. Thompson, Guillermo A. Zeballos, andMichael H. Gewitz. Role of inhibition of nitric oxide productionin monocrotaline-induced pulmonary hypertension. J. Appl. Physiol. 82(5): 1493-1498, 1997.Monocrotaline (MCT)-induced pulmonary hypertension (PH) isassociated with impaired endothelium-dependent nitric oxide(NO)-mediated relaxation. To examine the role of NO in PH,Sprague-Dawley rats were given a single subcutaneous injection ofnormal saline [control (C)], 80 mg/kg MCT, or the same doseof MCT and a continuous subcutaneous infusion of 2 mg · kg¹ · day¹of molsidomine, a NO prodrug (MCT+MD). Two weeks later, plasma NO₃ levels, pulmonary arterialpressure (Ppa), ratio of right-to-left ventricular weights (RV/LV) toassess right ventricular hypertrophy, and pulmonary histology wereevaluated. The plasma NO₃ level inthe MCT group was reduced to 9.2 ± 1.5 µM(n = 12) vs. C level of 17.7 ± 1.8 µM (n = 8; P < 0.02). In the MCT+MD group,plasma NO₃ level was 12.3 ± 2.0 µM (n = 8). Ppa and RV/LV in theMCT group were increased compared with C [Ppa, 34 ± 3.4 mmHg(n = 6) vs. 19 ± 0.8 mmHg(n = 8) and 0.41 ± 0.01 (n = 9) vs. 0.25 ± 0.008 (n = 8), respectively;P < 0.001]. In the MCT+MDgroup, Ppa and RV/LV were not different when compared with C [19 ± 0.5 mmHg (n = 5) and 0.27 ± 0.01 (n = 9), respectively;P < 0.001 vs. MCT]. Medial wall thickness of lung vessels in the MCT group was increased comparedwith C [31 ± 1.5% (n = 9)vs. 13 ± 0.66% (n = 9);P < 0.001], and MDpartially prevented MCT-induced pulmonary vascular remodeling [22 ± 1.2% (n = 11);P < 0.001 vs. MCT and C].These results indicate that a defect in the availability of bioactive NO may play an important role in the pathogenesis of MCT-induced PH.

     

Nitric oxide donors can increase heart rate independent of autonomic activation

Administration ofnitric oxide (NO) donors in vivo is accompanied by abaroreflex-mediated increase in heart rate (HR). In vitro, however, NOdonors can increase HR directly by stimulating a pathway that involvesNO, cGMP, and the hyperpolarization-activated current(I_f). The aimof this study was to assess the functional significance of this pathwayin vivo by testing whether NO donors can increase HR in theanesthetized rabbit independent of the autonomic nervous system. NewZealand White rabbits were vagotomized, cardiac sympathectomized, andtreated with propranolol (0.3 mg/kg iv). The NO donor molsidomine (0.2 mg/kg iv) caused a progressive increase () in HR (HR, 14 ± 3 beats/min; P < 0.01). This effect was significantly reduced by theI_f blockerZD-7288 (0.2 mg/kg iv; HR, 2 ± 3 beats/min;P = not significant).Similar results were seen with sodium nitroprusside. The positivechronotropic effect of sodium nitroprusside (50 µM) was confirmed inthe isolated working rabbit heart preparation (HR, 17 ± 3 beats/min; P < 0.01). In conclusion,NO donors exert a small, but significant, positive chronotropic effectin vivo that is independent of the autonomic nervous system. Theseresults are also consistent with data in sinoatrial node cells thatshow that NO donors increase HR by stimulatingI_f.

     

Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight

Fritsch-Yelle, Janice M., Peggy A. Whitson, Roberta L. Bondar, and Troy E. Brown. Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight.J. Appl. Physiol. 81(5):2134-2141, 1996.Postflight orthostatic intolerance isexperienced by virtually all astronauts but differs greatly in degreeof severity. We studied cardiovascular responses to upright posture in40 astronauts before and after spaceflights lasting up to 16 days. Weseparated individuals according to their ability to remain standingwithout assistance for 10 min on landing day. Astronauts who could notremain standing on landing day had significantly smaller increases inplasma norepinephrine levels with standing than did those who couldremain standing (105 ± 41 vs. 340 ± 62 pg/ml;P = 0.05). In addition, they hadsignificantly lower standing peripheral vascular resistance (23 ± 3 vs. 34 ± 3 mmHg ^· l^{1 ·} min;P = 0.02) and greater decreases insystolic (28 ± 4 vs. 11 ± 3 mmHg;P = 0.002) and diastolic (14 ± 7 vs. 3 ± 2 mmHg; P = 0.0003) pressures. The presyncopal group also hadsignificantly lower supine (16 ± 1 vs. 21 ± 2 mmHg ^· l^{1 ·} min;P = 0.04) and standing (23 ± 2 vs.32 ± 2 mmHg ^· l^{1 ·} min;P = 0.038) vascular resistance, supine(66 ± 2 vs. 73 ± 2 mmHg; P = 0.008) and standing (69 ± 4 vs. 77 ± 2 mmHg;P = 0.007) diastolic pressure, andsupine (109 ± 3 vs. 114 ± 2 mmHg; P = 0.05) and standing (99 ± 4 vs. 108 ± 3 mmHg; P = 0.006) systolic pressures before flight. This is the first study toclearly document these differences among presyncopal and nonpresyncopalastronauts after spaceflight and also offer the possibility ofpreflight prediction of postflight susceptibility. These resultsclearly point to hypoadrenergic responsiveness, possibly centrallymediated, as a contributing factor in postflight orthostaticintolerance. They may provide insights into autonomic dysfunction inEarthbound patients.

     

Intracerebroventricular propranolol prevented vascular resistance increases on arousal from sleep apnea

Zinkovska, Sophia, and Debra A. Kirby.Intracerebroventricular propranolol prevented vascular resistanceincreases on arousal from sleep apnea. J. Appl.Physiol. 82(5): 1637-1643, 1997.Despite theincreased risk of sudden cardiac death associated with sleep apnea,little is known about mechanisms controlling cardiovascular responsesto sleep apnea and arousal. Chronically instrumented pigs were used toinvestigate the effects of airway obstruction (AO) duringrapid-eye-movement (REM) and non-REM (NREM) sleep and arousal on meanarterial pressure (MAP), heart rate (HR), cardiac output (CO), andtotal peripheral resistance (TPR). A stainless steelcannula was implanted in the lateral cerebral ventricle. During REMsleep, HR was 133 ± 10 beats/min, MAP was 65 ± 3 mmHg, CO was1,435 ± 69 ml/min, and TPR was 0.046 ± 0.004 mmHg · ml¹ · min.During AO, CO decreased by 90 ± 17 ml/min(P < 0.05). On arousal from AO, MAPincreased by 15 ± 3 mmHg, HR increased by 10 ± 3 beats/min, andTPR increased by 0.008 ± 0.001 mmHg · ml¹ · min(all P < 0.05). Changes during NREMwere similar but were more modest during AO. After theintracerebroventricular administration of propranolol (50 µg/kg; a-adrenoreceptor blocking agent), decreases in CO during AO andincreases in HR during arousal were intact, but increases in MAP andTPR were no longer significant. These data suggest thatvascular responses to AO during sleep may be regulated in part by-adrenergic receptors in the central nervous system.

     

Atrial distension in humans during microgravity induced by parabolic flights

Videbaek, Regitze, and Peter Norsk. Atrialdistension in humans during microgravity induced by parabolic flights.J. Appl. Physiol. 83(6):1862-1866, 1997.The hypothesis was tested that human cardiacfilling pressures increase and the left atrium is distended during 20-speriods of microgravity (µG) created by parabolic flights, comparedwith values of the 1-G supine position. Left atrial diameter(n = 8, echocardiography) increasedsignificantly during µG from 26.8 ± 1.2 to 30.4 ± 0.7 mm(P < 0.05). Simultaneously, centralvenous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 ± 1.5 to 4.5 ± 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from1.5 ± 1.6 to 4.1 ± 1.7 mmHg (P < 0.05). Thus transmural CVP(TCVP = CVP  EP; n = 4)increased during µG from 6.1 ± 3.2 to 10.4 ± 2.7 mmHg(P < 0.05). It is concluded thatshort periods of µG during parabolic flights induce an increase inTCVP and left atrial diameter in humans, compared with the resultsobtained in the 1-G horizontal supine position, despite a decrease inCVP.

     

Supraglottic airway pressure-flow relationships during oronasal airflow partitioning in dogs

Amis, T. C., N. O'Neill, T. Van der Touw, A. Tully, and A. Brancatisano. Supraglottic airway pressure-flow relationships during oronasal airflow partitioning in dogs. J. Appl.Physiol. 81(5): 1958-1964, 1996.We studiedpressure-flow relationships in the supraglottic airway of eight pronemouth-open anesthetized (intravenous chloralose or pentobarbitalsodium) crossbred dogs (weight 15-26 kg) during increasingrespiratory drive (CO₂administration; n = 4) and duringgraded-voltage electrical stimulation (SV;n = 4) of the soft palate muscles.During increased respiratory drive, inspiratory airflow occurred viaboth the nose (n) and mouth(m), with the ratio of n tom[%(n/m)]decreasing maximally from 16.0 ± 7.0 (SD) to 2.4 ± 1.6%(P < 0.05). Simultaneously, oralairway resistance at peak inspiratory flow decreased from 2.1 ± 1.0 to 0.4 ± 0.4 cmH₂O(P < 0.05), whereas nasal airway resistance did not change (14.4 ± 7.2 to 13.1 ± 5.4 cmH₂O;P = 0.29). Inspiratory pressure-flowplots of the oral airway were inversely curvilinear or more complex innature. Nasal pathway plots, however, demonstrated a positive linearrelationship in all animals (r = 0.87 ± 0.11; all P < 0.001). Duringelectrical stimulation of soft palate muscle contraction accompanied bygraded constant-inspiratory airflows of 45-385 ml/s through anisolated upper airway, %(n/m)decreased from 69 ± 50 to 10 ± 13% at a SV of 84 ± 3% ofmaximal SV (P < 0.001). At a SV of85 ± 1% of maximum, normalized oral airway resistance (expressedas percent baseline) fell to 5 ± 3%, whereas normalized nasalresistance was 80 ± 9% (both P < 0.03). Thus control of oronasal airflow partitioning in dogsappears mediated more by alterations in oral route geometry than byclosure of the nasopharyngeal airway.

     

Contribution of nitric oxide and prostaglandins to reactive hyperemia in the human forearm

Engelke, Keith A., John R. Halliwill, David N. Proctor, NikiM. Dietz, and Michael J. Joyner. Contribution of nitric oxide andprostaglandins to reactive hyperemia in the human forearm. J. Appl. Physiol. 81(4):1807-1814, 1996.We investigated the separate and combinedcontributions of nitric oxide (NO) and vasodilating prostaglandins asmediators of reactive hyperemia in the human forearm. Forearm bloodflow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol (n = 12), measurements were made before and after intra-arterialadministration of the NO synthase inhibitorN^G-monomethyl-L-arginine(L-NMMA) to one forearm. In aseparate protocol (n = 7),measurements were made before and after systemic administration of thecyclooxygenase inhibitor ibuprofen and again afterL-NMMA.L-NMMA reduced baseline FBF atrest (2.7 ± 0.4 to 1.6 ± 0.2 ml ^· 100 ml^{1 ·} min¹;P < 0.05) and had a modesteffect on peak forearm vascular conductance and flow (forearm vascularconductance = 31.1 ± 3.1 vs. 25.7 ± 2.5 ml ^· min^{1 ·} 100 mlforearm^{1 ·} 100 mmHg of perfusionpressure^{1 ·} min¹,P < 0.05; FBF = 26.6 ± 2.9 vs.22.8 ± 2.6 ml ^· 100 ml^{1 ·} min¹,P = 0.055). Total excessflow above baseline during reactive hyperemia was unaffected byL-NMMA (14.3 ± 3.0 vs. 13.1 ± 2.3 ml/100 ml; P < 0.05).Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 ± 1.9 to 20.3 ± 2.7 ml ^· 100 ml^{1 ·} min¹(P < 0.05), but had no effect ontotal excess flow above baseline. Infusion ofL-NMMA after ibuprofen reducedFBF at rest by 40%, had no effect on peak flow, but reduced totalexcess flow above baseline from 12.0 ± 2.5 to 7.6 ± 1.3 ml/100ml (P < 0.05). These datademonstrate that NO synthase inhibition has a modest effect on peakvasodilation during reactive hyperemia but plays a minimal role later.Prostaglandins appear to be important determinants of peak flow. Theeffects of NO synthase inhibition during reactive hyperemia may also bepotentiated by concurrent cyclooxygenase inhibition.

     

Protective effects of intravascular pressure and nitric oxide in ischemic lung injury

Cessation of bloodflow during ischemia will decrease both distending and shearforces exerted on endothelium and may worsen ischemic lung injury bydecreasing production of nitric oxide (NO), which influences vascularbarrier function. We hypothesized that increased intravascular pressure(Piv) during ventilated ischemia might maintain NO productionby increasing endothelial stretch or shear forces, thereby attenuatingischemic lung injury. Injury was assessed by measuring the filtrationcoefficient(K_f) and theosmotic reflection coefficient for albumin(_alb) after 3 h of ventilated(95% O₂-5%CO₂; expiratory pressure 3 mmHg) ischemia. Lungs were flushed with physiological salt solution, and then Piv was adjusted to achieve High Piv (mean 6.7 ± 0.4 mmHg, n = 15) or Low Piv (mean0.83 ± 0.4 mmHg, n = 10).N^G-nitro-L-arginine methyl ester(L-NAME;10⁵ M,n = 10),N^G-nitro-D-argininemethyl ester (D-NAME;10⁵ M,n = 11), orL-NAME(10⁵M)+L-arginine (5 × 10⁴ M,n = 6) was added at the start ofischemia in three additional groups of lungs with High Piv.High Piv attenuated ischemic injury compared with Low Piv(_alb 0.67 ± 0.04 vs. 0.35 ± 0.04, P < 0.05). Theprotective effect of High Piv was abolished byL-NAME(_alb 0.37 ± 0.04, P < 0.05) but not byD-NAME(_alb 0.63 ± 0.07). The effects of L-NAME were overcomeby an excess of L-arginine(_alb 0.56 ± 0.05, P < 0.05).K_f did not differsignificantly among groups. These results suggest that Piv modulatesischemia-induced barrier dysfunction in the lung, and theseeffects may be mediated by NO.

     

Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans

We tested the hypothesis that the slowerincrease in alveolar oxygen uptake(O₂) at the onset ofsupine, compared with upright, exercise would be accompanied by aslower rate of increase in leg blood flow (LBF). Seven healthy subjectsperformed transitions from rest to 40-W knee extension exercise in theupright and supine positions. LBF was measured continuously with pulsedand echo Doppler methods, andO₂ was measured breath bybreath at the mouth. At rest, a smaller diameter of thefemoral artery in the supine position(P < 0.05) was compensated by agreater mean blood flow velocity (MBV) (P < 0.05) so that LBF was not different in the two positions. At the end of6 min of exercise, femoral artery diameter was larger in the uprightposition and there were no differences inO₂, MBV, or LBF betweenupright and supine positions. The rates of increase ofO₂ and LBF in thetransition between rest and 40 W exercise, as evaluated by the meanresponse time (time to 63% of the increase), were slower in the supine[O₂ = 39.7 ± 3.8 (SE) s, LBF = 27.6 ± 3.9 s] than in the uprightpositions (O₂ = 29.3 ± 3.0 s, LBF = 17.3 ± 4.0 s;P < 0.05). These data support ourhypothesis that slower increases in alveolarO₂ at the onset of exercisein the supine position are accompanied by a slower increase in LBF.