Exercise attenuates {alpha}-adrenergic-receptor responsiveness in skeletal muscle vasculature

Attenuation of sympathetic vasoconstriction(sympatholysis) in working muscles during dynamic exercise iscontroversial. A potential mechanism is a reduction in-adrenergic-receptor responsiveness. The purpose of this study wasto examine ₁- and ₂-adrenergic-receptor-mediated vasoconstriction inresting and exercising skeletal muscle using intra-arterial infusionsof selective agonists. Thirteen mongrel dogs were instrumentedchronically with flow probes on the external iliac arteries of bothhindlimbs and a catheter in one femoral artery. The selective₁-adrenergic agonist (phenylephrine) or the selective₂-adrenergic agonist (clonidine) was infused as a bolusinto the femoral artery catheter at rest and during mild and heavyexercise. Intra-arterial infusions of phenylephrine elicited reductionsin vascular conductance of 76 ± 4, 71 ± 5, and 31 ± 2% at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively.Intra-arterial clonidine reduced vascular conductance by 81 ± 5, 49 ± 4, and 14 ± 2%, respectively. The response tointra-arterial infusion of clonidine was unaffected by surgicalsympathetic denervation. Agonist infusion did not affect eithersystemic blood pressure, heart rate, or blood flow in the contralateraliliac artery. ₁-Adrenergic-receptor responsiveness wasattenuated during heavy exercise. In contrast,₂-adrenergic-receptor responsiveness was attenuated evenat a mild exercise intensity. These results suggest that the mechanismof exercise sympatholysis may involve reductions in postsynaptic-adrenergic-receptor responsiveness.

     

Renal hemodynamic responses to dynamic exercise in rabbits

Cardiovascular hemodynamics, including renalblood flow, were measured in rabbits with one intact and one denervatedkidney during various intensities of treadmill exercise. Within thefirst 10 s of exercise, there was rapid vasoconstriction in theinnervated kidney associated with decreases in renal blood flow (range10 to 17%). The vasoconstriction in the innervatedkidney was evident at all workloads and was intensity dependent. Therewas no significant vasoconstriction or change in renal blood flow(range 0.5 to 3.1%) in the denervated kidney at the onset ofexercise. However, a slowly developing vasoconstriction occurred in thedenervated kidney as exercise progressed to 2 min at all workloads.Examination of responses to exercise performed under -adrenergicblockade with phentolamine (5 mg/kg iv) revealed that thevasoconstriction in the innervated kidney at the onset of exercise andthe delayed vasoconstriction in the denervated kidney were dueprimarily to activation of -adrenergic receptors. Inaddition, a residual vasoconstriction was also present in theinnervated kidney after -adrenergic blockade, suggesting that,during exercise, activation of other renal vasoconstrictor mechanismsoccurs which is dependent on the presence of renal nerves.

     

Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers

Migita, Russell, Armando Gonzales, Maria L. Gonzales, Kim D. Vandegriff, and Robert M. Winslow. Blood volume and cardiac indexin rats after exchange transfusion with hemoglobin-based oxygencarriers. J. Appl. Physiol. 82(6):1995-2002, 1997.We have measured plasma volume and cardiac indexin rats after 50% isovolemic exchange transfusion with humanhemoglobin cross-linked between the -chains withbis(3,5-dibromosalicyl)fumarate (Hb) and with bovine hemoglobinmodified with polyethylene glycol (PEGHb). Hb and PEGHb differ incolloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygenaffinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), andmolecular weight (64,400 and 105,000, respectively). Plasma volume wasmeasured by Evans blue dye dilution modified for interference by plasmahemoglobin. Blood volumes in PEGHb-treated animals were significantlyelevated (74.0 ± 3.5 ml/kg) compared with animals treated withHb (49.0 ± 1.2 ml/kg) or Ringer lactate (48.0 ± 2.0 ml/kg) or with controls (58.2 ± 1.9 ml/kg). Heart rate reductionafter Hb exchange is opposite to that expected with blood volumecontraction, suggesting that Hb may have a direct myocardialdepressant action. The apparently slow elimination of PEGHb during the2 h after its injection is a consequence of plasma volume expansion:when absolute hemoglobin (concentration × plasma volume) iscompared for PEGHb and Hb, no difference in their eliminationrates is found. These studies emphasize the need to understand bloodvolume regulation when the effects of cell-free hemoglobin onhemodynamic measurements are evaluated.

     

Catecholamine responses to {alpha}-adrenergic blockade during exercise in women acutely exposed to altitude

We have previouslydocumented the importance of the sympathetic nervous system inacclimatizing to high altitude in men. The purpose ofthis investigation was to determine the extent to which -adrenergicblockade affects the sympathoadrenal responses to exercise during acutehigh-altitude exposure in women. Twelve eumenorrheic women (24.7 ± 1.3 yr, 70.6 ± 2.6 kg) were studied at sea level and onday 2 of high-altitude exposure (4,300-m hypobaric chamber)in either their follicular or luteal phase. Subjects performed twograded-exercise tests at sea level (on separate days) on a bicycleergometer after 3 days of taking either a placebo or an -blocker (3 mg/day prazosin). Subjects also performed two similar exercise testswhile at altitude. Effectiveness of blockade was determined byphenylephrine challenge. At sea level, plasma norepinephrine levelsduring exercise were 48% greater when subjects were -blockedcompared with their placebo trial. This difference was only 25% whensubjects were studied at altitude. Plasma norepinephrine values weresignificantly elevated at altitude compared with sea level but to agreater extent for the placebo (59%) vs. blocked (35%) trial. Amore dramatic effect of both altitude (104% placebo vs. 95%blocked) and blockade (50% sea level vs. 44% altitude) wasobserved for plasma epinephrine levels during exercise. No phasedifferences were observed across any condition studied. It wasconcluded that -adrenergic blockade 1) resulted in acompensatory sympathoadrenal response during exercise at sea level andaltitude, and 2) this effect was more pronounced for plasma epinephrine.

     

Muscle chemoreflex increases renal sympathetic nerve activity during exercise

O'Hagan, Kathleen P., Susan M. Casey, and Philip S. Clifford. Muscle chemoreflex increases renalsympathetic nerve activity during exercise. J. Appl.Physiol. 82(6): 1818-1825, 1997.Activation ofthe muscle chemoreflex increases sympathetic drive to skeletal musclein humans. This study investigated whether activation of the musclechemoreflex augments the renal sympathetic nerve activity (RSNA)response to dynamic exercise in rabbits. The muscle chemoreflex wasevoked by hindlimb ischemia during exercise on a motorized treadmill.Seven New Zealand White rabbits performed a nonischemic controlprotocol and a hindlimb ischemia protocol in which terminal aorticblood flow (ta) was reduced to 51 ± 2% ofpreocclusion ta by partial aortic occlusion after 1.5 min of exercise. Mean arterial pressure (MAP), heart rate, RSNA andta increased in response to exercise and weresimilar between trials during the first 1.5 min of exercise. In thecontrol trial, ta, MAP, and RSNA were stable at anelevated level through an additional 3.5 min of exercise. Hindlimbischemia produced a potent pressor response that plateaued after 2.5 min (+17 ± 4 mmHg, where  designates change). RSNA began toincrease after 1.5 min of ischemic exercise and was significantlyelevated relative to preocclusion RSNA at 2.5 (+25 ± 9%) and3.5 (+47 ± 12%) min of occlusion. These results suggest thatthe muscle chemoreflex can augment sympathoexcitatory drive to thekidney during dynamic exercise.

     

alpha 1-Adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise

Attenuation of sympathetic vasoconstriction(sympatholysis) in working muscles during dynamic exercise iscontroversial. One potential mechanism is a reduction in₁-adrenergic-receptorresponsiveness. The purpose of this study was to examine₁-adrenergic-receptor-mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective agonist. Seven mongrel dogswere instrumented chronically with flow probes on the external iliacarteries of both hindlimbs and a catheter in one femoral artery. Aselective ₁-adrenergic-receptoragonist (phenylephrine) was infused as a bolus into the femoral arterycatheter at rest and during exercise. All dogs ran on amotorized treadmill at two exercise intensities (3 and 6 miles/h).Intra-arterial infusions of the same effective concentration ofphenylephrine elicited reductions in vascular conductance of 76 ± 4, 76 ± 6, and 67 ± 5% (P > 0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic bloodpressure and blood flow in the contralateral iliac artery wereunaffected by phenylephrine. These results do not demonstrate anattenuation of vasoconstriction to a selective ₁-agonist during exercise anddo not support the concept of sympatholysis.

     

O2 uptake kinetics after acetazolamide administration during moderate- and heavy-intensity exercise

Inhibition of carbonic anhydrase (CA) isassociated with a lower plasma lactate concentration([La]_pl)during fatiguing exercise. We hypothesized that a lower[La]_plmay be associated with faster O₂uptake (O₂) kinetics during constant-load exercise. Seven men performed cycle ergometer exercise during control (Con) and acute CA inhibition with acetazolamide (Acz,10 mg/kg body wt iv). On 6 separate days, each subject performed 6-minstep transitions in work rate from 0 to 100 W (below ventilatory threshold,<ET)or to a O₂ corresponding to~50% of the difference between the work rate atET and peakO₂(>ET).Gas exchange was measured breath by breath. Trials were interpolated at1-s intervals and ensemble averaged to yield a single response. The mean response time (MRT, i.e., time to 63% of total exponential increase) for on- and off-transients was determined using a two- (<ET) or athree-component exponential model(>ET).Arterialized venous blood was sampled from a dorsal hand vein andanalyzed for[La]_pl.MRT was similar during Con (31.2 ± 2.6 and 32.7 ± 1.2 s for onand off, respectively) and Acz (30.9 ± 3.0 and 31.4 ± 1.5 s for on and off, respectively) for work rates<ET. Atwork rates >ET, MRTwas similar between Con (69.1 ± 6.1 and 50.4 ± 3.5 s for on andoff, respectively) and Acz (69.7 ± 5.9 and 53.8 ± 3.8 s for on and off, respectively). On- and off-MRTs were slower for>ET thanfor <ETexercise.[La]_plincreased above 0-W cycling values during<ET and>ET exercise but was lower at the end of the transition during Acz (1.4 ± 0.2 and 7.1 ± 0.5 mmol/l for<ET and>ET,respectively) than during Con (2.0 ± 0.2 and 9.8 ± 0.9 mmol/lfor <ETand >ET,respectively). CA inhibition does not affectO₂ utilization at the onset of<ET or>ETexercise, suggesting that the contribution of oxidative phosphorylationto the energy demand is not affected by acute CA inhibition with Acz.

     

Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments

Rudolph, Alan S., Anthony Sulpizio, Paul Hieble, VictorMacdonald, Mark Chavez, and Giora Feuerstein. Liposomeencapsulation attenuates hemoglobin-induced vasoconstriction in rabbitarterial segments. J. Appl. Physiol.82(6): 1826-1835, 1997.Free hemoglobin (Hb) induces a potentvasoconstrictor response that may limit its therapeutic application asa red blood cell replacement. We have investigated whetherencapsulation of stroma-free Hb (SFHb) or cross-linked Hb (-Hb)in liposomes modulates Hb vasoactivity in isolated blood vessels.Relaxation of rabbit thoracic vessels was measured before and afterexposure to acellular SFHb, -Hb, and liposome-encapsulated SFHbor -Hb. SFHb and -Hb caused significant inhibition ofcarbachol-induced relaxation at 0.5 mg/dl, whereas encapsulationinhibited vessel relaxation at 30- to 60-fold higher Hb concentrations.The contractile response of rabbit ear arterial segments to electricalstimulation in the presence of acellular -Hb resulted in a 150%increase (EC₁₅₀) in contractileamplitude at 0.23 mg/dl, whereas theEC₁₅₀ for encapsulated -Hbwas 13.7 mg/dl. Mechanistic studies of the vasoconstrictor activity ofHb demonstrated that acellular -Hb had no effect onnorepinephrine release in the rabbit ear artery. In addition, neitheracellular nor encapsulated -Hb preparations inhibited endothelialnitric oxide (NO) synthase activity isolated from bovine pulmonaryartery. However, inhibition of vessel relaxation by acellular orencapsulated -Hb was reversed by the NO donor S-nitrosylpenacillamine, implicatingHb-NO binding as a possible mechanism for the vasoconstrictor response.In vitro stopped-flow kinetic studies of Hb-NO binding showed similarrates of reaction for conversion of oxyhemoglobin to methemoglobin(metHb; <2 ms), followed by rapid conversion of metHb to NO-Hb (300 ms) for both acellular and encapsulated -Hb, demonstrating thatliposome encapsulation does not retard NO-Hb binding. The attenuatedvasoactivity of encapsulated Hb may, therefore, result from the limitedaccess of encapsulated Hb to NO imposed by the physical size of theliposome and reduced penetration of Hb across the vascular endothelium.

     

Combined heart rate and activity improve estimates of oxygen consumption and carbon dioxide production rates

Moon, Jon K., and Nancy F. Butte. Combined heart rateand activity improve estimates of oxygen consumption and carbon dioxideproduction rates. J. Appl. Physiol.81(4): 1754-1761, 1996.Oxygen consumption(O₂) andcarbon dioxide production (CO₂) rates were measuredby electronically recording heart rate (HR) and physical activity (PA).Mean daily O₂ andCO₂ measurements by HR andPA were validated in adults (n = 10 women and 10 men) with room calorimeters. Thirteen linear and nonlinear functions of HR alone and HR combined with PA were tested as models of24-h O₂ andCO₂. Mean sleepO₂ andCO₂ were similar to basalmetabolic rates and were accurately estimated from HR alone[respective mean errors were 0.2 ± 0.8 (SD) and0.4 ± 0.6%]. The range of prediction errorsfor 24-h O₂ andCO₂ was smallestfor a model that used PA to assign HR for each minute to separateactive and inactive curves(O₂, 3.3 ± 3.5%; CO₂, 4.6 ± 3%). There were no significant correlations betweenO₂ orCO₂ errors and subject age,weight, fat mass, ratio of daily to basal energy expenditure rate, orfitness. O₂,CO₂, and energy expenditurerecorded for 3 free-living days were 5.6 ± 0.9 ml ^· min^{1 ·} kg¹,4.7 ± 0.8 ml ^· min^{1 ·} kg¹,and 7.8 ± 1.6 kJ/min, respectively. Combined HR and PA measured 24-h O₂ andCO₂ with a precisionsimilar to alternative methods.

     

Importance of the lactate anion in control of breathing

Hardarson, Thorir, Jon O. Skarphedinsson, and TorarinnSveinsson. Importance of the lactate anion in control ofbreathing. J. Appl. Physiol. 84(2):411-416, 1998.The purpose of this study was to examine theeffects of raising the arterialLa andK⁺ levels on minute ventilation(E) in rats. EitherLa or KCl solutions wereinfused in anesthetized spontaneously breathing Wistar rats to raisethe respective ion arterial concentration ([La] and[K⁺]) gradually tolevels similar to those observed during strenuous exercise.E, blood pressure, and heart rate wererecorded continuously, and arterial[La],[K⁺], pH, and bloodgases were repeatedly measured from blood samples. To prevent changesin pH during the Lainfusions, a solution of sodium lactate and lactic acid was used. Raising [La] to13.2 ± 0.6 (SE) mM induced a 47.0 ± 4.0% increase inE without any concomitant changes ineither pH or PCO₂. Raising[K⁺] to 7.8 ± 0.11 mM resulted in a 20.3 ± 5.28% increase inE without changes in pH. Thus ourresults show that Laitself, apart from lactic acidosis, may be important in increasing E during strenuous exercise, and weconfirm earlier results regarding the role of arterial[K⁺] in the control ofE during exercise.

     

Improved oxygenation with prostaglandin F2alpha with and without inhaled nitric oxide in dogs

Dogs of mixedbreed (n = 7) were anesthetized, rightlung atelectasis was established, and the cyclooxygenase pathway was blocked with ibuprofen. Measurements of pulmonary gas exchange wereperformed (fractional concentration of inspiredO₂ = 0.95) after infusions ofprostaglandin F₂(PGF₂; 2 µg · kg¹ · min¹),ventilation with nitric oxide (NO; 40 ppm), or both(PGF₂ + NO) in random order.The arterial PO₂(Pa_O2) under control conditions was 117 ± 16 Torr (shunt = 33 ± 2.5%), was unchanged with NO alone(Pa_O2 = 114 ± 17 Torr; shunt = 35.7 ± 3.1%), but was significantlyimproved with PGF₂ alone(Pa_O2 = 180 ± 28 Torr; shunt = 23.2 ± 2.8%) and with the combination ofPGF₂ + NO(Pa_O2 = 202 ± 30 Torr; shunt = 20.9 ± 2.5%). The addition of NO didnot significantly enhance the effectiveness of thePGF₂ onPa_O2.Simulation of these data in a computer model, combining pulmonary gasexchange and pulmonary blood flow, reproduced the results on the basisthat vasoconstriction with PGF₂was maximal under hypoxia in the atelectatic lung and reduced byhyperoxia in the ventilated lung, consistent with the hypothesis ofO₂ dependence ofPGF₂ vasoconstriction.

     

Kinetics of oxygen uptake at the onset of exercise in boys and men

The objective of this study was to compare theO₂ uptake(O₂) kinetics at the onsetof heavy exercise in boys and men. Nine boys, aged 9-12 yr, and 8 men, aged 19-27 yr, performed a continuous incremental cyclingtask to determine peak O₂(O_{2 peak}).On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice bycycling at 50%O_{2 peak} for 3.5 min,once by cycling at 100%O_{2 peak} for 2 min,and once by cycling at 130%O_{2 peak} for 75 s.O₂ deficit was not significantlydifferent between boys and men (respectively, 50%O_{2 peak} task: 6.6 ± 11.1 vs. 5.5 ± 7.3 ml · min¹ · kg¹;100% O_{2 peak} task:28.5 ± 8.1 vs. 31.8 ± 6.3 ml · min¹ · kg¹;and 130%O_{2 peak}task: 30.1 ± 5.7 vs. 35.8 ± 5.3 ml · min¹ · kg¹).To assess the kinetics, phase I was excluded from analysis. Phase IIO₂ kinetics could bedescribed in all cases by a monoexponential function. ANOVA revealed nodifferences in time constants between boys and men (respectively, 50%O_{2 peak}task: 22.8 ± 5.1 vs. 26.4 ± 4.1 s; 100%O_{2 peak} task: 28.0 ± 6.0 vs. 28.1 ± 4.4 s; and 130%O_{2 peak} task: 19.8 ± 4.1 vs. 20.7 ± 5.7 s). In conclusion, O₂ deficit and fast-componentO₂ on-transientsare similar in boys and men, even at high exercise intensities, whichis in contrast to the findings of other studies employing simplermethods of analysis. The previous interpretation that children relyless on nonoxidative energy pathways at the onset of heavy exercise isnot supported by our findings.

     

Mechanisms of ventilatory inhibition by exogenous dopamine in cats

Intravenous injection of dopamine (DA) hasconsistently been shown to depress minute ventilation(E). Whereas at low dosage (10µg/kg) this effect may be accounted for by inhibition of the carotidsinus nerve chemosensory discharge (CSNCD), other mechanisms appear tobe involved with large dosage (50 µg/kg). The purpose of this studywas to elucidate the mechanisms of DA-induced E depression. The effects ofintravenous injection of DA doses ranging from 1 to 200 µg/kg werestudied in 18 anesthetized cats. DA was injected during air andO₂ breathing, after -adrenergic blockade by phenoxybenzamine and after baro- and chemodenervation. E and CSNCD were also simultaneouslyrecorded on four occasions. In contrast to that with use of low-doseDA, E depression induced by high-doseDA was dissociated from CSNCD, persisted during 100% O₂ breathing, and wassignificantly correlated with the rise in arterial blood pressure.Although blunted, E depression was still present after complete chemo- and barodenervation but was suppressed by blocking of the concomitant vasoconstriction with phenoxybenzamine. It is concluded that reflexes of circulatory origincontribute to the E depression inducedby large-dose DA, in addition to its effects on arterialchemoreceptors. The contribution of baroreceptor stimulation andperipheral vasoconstriction is discussed.

     

Age-related declines in maximal aerobic capacity in regularly exercising vs. sedentary women: a meta-analysis

Fitzgerald, Margaret D., Hirofumi Tanaka, Zung V. Tran, andDouglas R. Seals. Age-related declines in maximal aerobic capacityin regularly exercising vs. sedentary women: a meta-analysis. J. Appl. Physiol. 83(1): 160-165, 1997.Our purpose was to determine the relationship between habitualaerobic exercise status and the rate of decline in maximal aerobiccapacity across the adult age range in women. A meta-analytic approachwas used in which mean maximal oxygen consumption(O_{2 max}) values fromfemale subject groups (ages 18-89 yr) were obtained from thepublished literature. A total of 239 subject groups from 109 studiesinvolving 4,884 subjects met the inclusion criteria and werearbitrarily separated into sedentary (groups = 107; subjects = 2,256),active (groups = 69; subjects = 1,717), and endurance-trained (groups = 63; subjects = 911) populations.O_{2 max} averaged 29.7 ± 7.8, 38.7 ± 9.2, and 52.0 ± 10.5 ml · kg¹ · min¹,respectively, and was inversely related to age within each population (r = 0.82 to 0.87, allP < 0.0001). The rate of decline inO_{2 max} withincreasing subject group age was lowest in sedentary women (3.5ml · kg¹ · min¹· decade¹), greater inactive women (4.4ml · kg¹ · min¹· decade¹), andgreatest in endurance-trained women (6.2ml · kg¹ · min¹ · decade¹)(all P < 0.001 vs. each other). Whenexpressed as percent decrease from mean levels at age ~25 yr, therates of decline inO_{2 max} were similarin the three populations (10.0 to 10.9%/decade). Therewas no obvious relationship between aerobic exercise status and therate of decline in maximal heart rate with age. The results of thiscross-sectional study support the hypothesis that, in contrast to theprevailing view, the rate of decline in maximal aerobic capacity withage is greater, not smaller, in endurance-trained vs. sedentary women.The greater rate of decline inO_{2 max} in endurance-trained populations may be related to their higher values asyoung adults (baseline effect) and/or to greater age-related reductions in exercise volume; however, it does not appear to berelated to a greater rate of decline in maximal heart rate with age.

     

Ventilatory response to exercise in diabetic subjects with autonomic neuropathy

Tantucci, C., P. Bottini, M. L. Dottorini, E. Puxeddu, G. Casucci, L. Scionti, and C. A. Sorbini. Ventilatory response toexercise in diabetic subjects with autonomic neuropathy.J. Appl. Physiol. 81(5):1978-1986, 1996.We have used diabetic autonomic neuropathy as amodel of chronic pulmonary denervation to study the ventilatoryresponse to incremental exercise in 20 diabetic subjects, 10 with(Dan+) and 10 without (Dan) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan subjectsachieved lower O₂ consumption andCO₂ production(CO₂) thancontrol subjects at peak of exercise, they attained similar values ofeither minute ventilation(E) oradjusted ventilation (E/maximalvoluntary ventilation). The increment of respiratory rate withincreasing adjusted ventilation was much higher in Dan+ than inDan and control subjects (P < 0.05). The slope of the linearE/CO₂relationship was 0.032 ± 0.002, 0.027 ± 0.001 (P < 0.05), and 0.025 ± 0.001 (P < 0.001) ml/min inDan+, Dan, and control subjects, respectively. Bothneuromuscular and ventilatory outputs in relation to increasingCO₂ were progressivelyhigher in Dan+ than in Dan and control subjects. At peak ofexercise, end-tidal PCO₂ was muchlower in Dan+ (35.9 ± 1.6 Torr) than in Dan (42.1 ± 1.7 Torr; P < 0.02) and control (42.1 ± 0.9 Torr; P < 0.005) subjects.We conclude that pulmonary autonomic denervation affects ventilatoryresponse to stressful exercise by excessively increasing respiratoryrate and alveolar ventilation. Reduced neural inhibitory modulationfrom sympathetic pulmonary afferents and/or increasedchemosensitivity may be responsible for the higher inspiratoryoutput.

     

Dynamic resistance exercise and resting blood pressure in adults: a meta-analysis

George, Kelley. Dynamic resistance exercise and restingblood pressure in adults: a meta-analysis. J. Appl.Physiol. 82(5): 1559-1565, 1997.With the use ofthe meta-analytic approach, the purpose of this study was to examinethe effects of dynamic resistance exercise, i.e., weight training, onresting systolic and diastolic blood pressure in adults. A total ofnine studies consisting of 259 subjects (144 exercise, 115 control) and18 groups (9 exercise, 9 control) were included in this analysis. Withthe use of the bootstrap technique (10,000 samples), significant treatment effect(₃)reductions were found across all designs and categories for bothsystolic and diastolic blood pressure [systolic, mean ± SD = 4.55 ± 1.75 mmHg, 95% confidence interval (CI) = 1.56 to 8.56; diastolic, mean ± SD = 3.79 + 1.12 mmHg, 95% confidence interval CI = 1.89 to6.33]. ₃ changescorresponded with relative decreases of ~3 and 4% in restingsystolic and diastolic blood pressure, respectively. Inconclusion, meta-analytic review of included studies suggests thatdynamic resistance exercise reduces resting systolic and diastolicblood pressure in adults. However, it is premature to form strongconclusions regarding the effects of dynamic resistance exercise onresting blood pressure. A need exists for additional, well-designedstudies on this topic before a recommendation can be made regarding theefficacy of dynamic resistance exercise as a nonpharmacological therapyfor reducing resting blood pressure in adults, especially inhypertensive adults.

     

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure

To simulate theimmediate hemodynamic effect of negative intrathoracic pressure duringobstructive apneas in congestive heart failure (CHF), without inducingconfounding factors such as hypoxia and arousals from sleep, eightawake patients performed, at random, 15-s Mueller maneuvers (MM) attarget intrathoracic pressures of 20 (MM 20) and40 cmH₂O (MM 40),confirmed by esophageal pressure, and 15-s breath holds, as apneic timecontrols. Compared with quiet breathing, at baseline, before theseinterventions, the immediate effects [first 5 cardiac cycles(SD), P values refer to MM 40compared with breath holds] of apnea, MM 20, and MM 40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 ± 1.9, 7.2 ± 3.5, and 11.3 ± 6.8 mmHg(P < 0.01); for systolic bloodpressure (SBP), 2.9 ± 2.6, 5.5 ± 3.4, and 12.1 ± 6.8 mmHg (P < 0.01); and forstroke volume (SV) index, 0.4 ± 2.8, 4.1 ± 2.8, and6.9 ± 2.3 ml/m²(P < 0.001), respectively.Corresponding values over the last five cardiac cycles were for LVPtm6.4 ± 4.4, 5.4 ± 6.6, and 4.5 ± 9.1 mmHg (P < 0.01); for SBP6.9 ± 4.2, 8.2 ± 7.7, and 24.2 ± 6.9 mmHg (P < 0.01); and for SVindex 0.4 ± 2.1, 5.2 ± 2.8, and 9.2 ± 4.8 ml/m²(P < 0.001), respectively.Thus, in CHF patients, the initial hemodynamic response to thegeneration of negative intrathoracic pressure includes an immediateincrease in LV afterload and an abrupt fall in SV. The magnitude ofresponse is proportional to the intensity of the MM stimulus. By theend of a 15-s MM 40, LVPtm falls below baseline values, yet SVand SBP do not recover. Thus, when 40cmH₂O intrathoracic pressure issustained, additional mechanisms, such as a drop in LV preload due toventricular interaction, are engaged, further reducing SV. The neteffect of MM 40 was a 33% reduction in SV index (from 27 to 18 ml/min²), and a 21% reductionin SBP (from 121 to 96 mmHg). Obstructive apneas can have adverseeffects on systemic and, possibly, coronary perfusion in CHF throughdynamic mechanisms that are both stimulus and timedependent.

     

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.

     

Activity of respiratory pump and upper airway muscles during sleep onset

Ventilationdecreases at sleep onset. This change is initiated abruptly at -electroencephalographic transitions. The aim of this study was todetermine the contributions of reduced activity in respiratory pumpmuscles and upper airway dilator muscles to this change. Surfaceelectromyograms over the diaphragm (Di) and intercostal muscles andfine-wire intramuscular electrodes in genioglossus (GG) and tensorpalatini (TP) muscles were recorded in nine healthy young men. It wasshown that phasic Di and both phasic and tonic TP activities were lowerduring  than during  activity. Breath-by-breath analysis of thechanges at - transitions during the sleep-onset period showed anumber of changes. At - transitions, phasic activity of Di,intercostal, and GG muscles fell and rose again, and phasic and tonicactivities of TP fell and remained at low levels during . With astate transition from  to , the phasic and tonic activities ofthe Di, GG, and TP increased dramatically. It is now clear that thefall in ventilation that occurs with sleep is related to a fall inactivities of both upper airway dilator muscles and respiratory pumpmuscles.

     

Nitric oxide and beta -adrenergic agonist-induced bronchial arterial vasodilation

Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan,William H. Thompson, and Paula Carvalho. Nitric oxide and-adrenergic agonist-induced bronchial arterial vasodilation.J. Appl. Physiol. 82(2): 686-692, 1997.In anesthetized sheep, we measured bronchial blood flow(br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) givenfor 5 min and 5 ml of aerosolized isoetharine (1.49 × 10² M concentration).NO and isoetharine increased br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min,respectively (n = 5).Administration of NO immediately after isoetharine further increasedbr to 57.3 ± 15.1 ml/min. NO synthase inhibitorN-nitro-L-arginine methyl esterhydrochloride (L-NAME; 30 mg/kg, in 20 ml salinegiven iv) decreased br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiatevasodilator effects of each other. In three other sheep, afterL-NAME, three sequential doses of isoetharine increased br from 10.2 ± 3.4 to11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min,respectively, indicating that effects of isoetharine are predominantlymediated through synthesis of NO. When this was followed by threesequential administrations of NO, br increased by146, 172, and 185%, respectively. Thus in the bronchial circulationthere seems to be a close interaction between adenosine3,5-cyclic monophosphate- and guanosine3,5-cyclic monophosphate-mediated vasodilatation.