Cerebral areas associated with motor control of speech in humans

Murphy, K., D. R. Corfield, A. Guz, G. R. Fink, R. J. S. Wise, J. Harrison, and L. Adams. Cerebral areas associated withmotor control of speech in humans. J. Appl.Physiol. 83(5): 1438-1447, 1997.We have definedareas in the brain activated during speaking, utilizing positronemission tomography. Six normal subjects continuously repeated thephrase "Buy Bobby a poppy" (requiring minimal languageprocessing) in four ways: A) spoken aloud, B) mouthed silently,C) without articulation, andD) thought silently. Statisticalcomparison of images from conditions Awith C andB withD highlighted areas associated witharticulation alone, because control of breathing for speech wascontrolled for; we found bilateral activations in sensorimotor cortexand cerebellum with right-sided activation in the thalamus/caudate nucleus. Contrasting images from conditionsA with B andC with D highlighted areas associated withthe control of breathing for speech, vocalization, and hearing, becausearticulation was controlled for; we found bilateral activations insensorimotor and motor cortex, close to but distinct from theactivations in the preceding contrast, together with activations inthalamus, cerebellum, and supplementary motor area. In neithersubtraction was there activation in Broca's area. These resultsemphasize the bilaterality of the cerebral control of "speaking"without language processing.

     

Scaling of submaximal oxygen uptake with body mass and combined mass during uphill treadmill bicycling

This study examined the scaling relationships ofnet O₂ uptake [O_2(net) = O₂  restingO₂] to body mass(M_B) andcombined mass (M_C = M_B + bicycle)during uphill treadmill bicycling. It was hypothesized thatO_2(net)(l/min) would scale proportionally withM_C [i.e.,O_2(net)  M^1.0_C] and less than proportionally withM_B [i.e.,O_2(net)  M_B].Twenty-five competitive cyclists [73.9 ± 8.8 and 85.0 ± 9.0 (SD) kg forM_B andM_C,respectively] rode their bicycles on a treadmill at 3.46 m/s andgrades of 1.7, 3.5, 5.2, and 7.0% whileO₂ was measured. Multiplelog-linear regression procedures were applied to the pooledO_2(net)data to determine the exponents forM_C andM_B afterstatistically controlling for differences in treadmill grade anddynamic friction. The regression models were highly significant (R² = 0.95, P < 0.001). Exponents forM_C (0.99, 95%confidence interval = 0.80-1.18) andM_B (0.89, 95%confidence interval = 0.72-1.07) did not differ significantly fromeach other or 1.0. It was concluded that the 0.99 M_C exponent wasdue to gravitational resistance, whereas theM_B exponent was<1.0 because the bicycles were relatively lighter for heaviercyclists.

     

Influence of group B streptococci on piglet pulmonary artery response to bradykinin

To study whether a sepsis-induced increase indes-Arg⁹-bradykinin(des-Arg⁹-BK) and bradykinin (BK)B₁-receptor activity participatesin the observed increase in pulmonary vascular resistance in neonatal group B streptococcal sepsis (GBS), isometric force bioassays ofpulmonary artery (PA) rings were studied, after 4-h exposure to eitherKrebs or GBS, by using the following protocols:1) BK dose-response curve,2) vascular response to BK withN^G-nitro-L-arginine methyl ester(L-NAME), and3) response todes-Arg⁹-BK (BK metabolite andB₁ agonist). PA rings exposed toBK resulted in contraction in the GBS group and a decrease in restingtension in the Control group (P = 0.034) at a concentration of10⁵ M. GBS-treated PA ringscontracted more to des-Arg⁹-BKthan did Controls (P < 0.001). BK(10⁶ M) relaxedpreconstricted PA rings incubated in GBS less than BK relaxed Controls(P < 0.001), and preincubation withL-NAME decreased relaxation inboth. These results suggest that GBS decreased endothelium-dependent BKrelaxation and increased contractile response todes-Arg⁹-BK. We speculate thatthis occurs secondary to upregulation of B₁ receptors reflected byB₁-agonist-mediated PA contraction.

     

Peroxynitrite and nitric oxide differ in their effects on pig coronary artery smooth muscle

Peroxynitrite generated in arteries fromsuperoxide and nitric oxide (NO) may damage their function. Here, wecompare the effects of peroxynitrite and peroxynitrite/NO-generatingagents SIN-1 (3-morpholinosydnonimine hydrochloride), SNAP(S-nitroso-N-acetyl-penicillamine), SNP (sodiumnitroprusside), and NONOate (spermine NONOate) on pig coronary artery.Deendothelialized artery rings were pretreated with these agents andthen washed before examining their contractility. Pretreatment with allagents (200 µM) results in a decrease in the force of contraction inresponse to the sarco(endo)plasmic Ca²⁺ (SERCA) pumpinhibitor cyclopiazonic acid (CPA): SNAP > NONOate  peroxynitrite  SIN-1 > SNP. Pretreatment with SNAP,NONOate, or SIN-1 also inhibits the force of contraction produced with 30 mM KCl, with SNAP being the most potent. Including catalase plussuperoxide dismutase (SOD) during the preincubation has no effect. Including an NO scavenger[2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] or a guanylate cyclase inhibitor(1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) partially protects against SNAP. Pretreatment of cultured cells with peroxynitrite, but not with SNAP, inhibits the Ca²⁺transients produced in response to CPA. Pretreating isolated membranevesicles with peroxynitrite inhibits the Ca²⁺ uptake due tothe SERCA pump, with all the other agents being less effective. Thusperoxynitrite and NO both inhibit the CPA-induced contractions indeendothelialized artery rings, peroxynitrite by damage to the SERCApump and NO possibly by a step downstream from the increase incytosolic Ca²⁺.

     

Regional measurements of pulmonary edema by using magnetic resonance imaging

Athree-dimensional magnetic resonance imaging (MRI) method to measurepulmonary edema and lung microvascular barrier permeability wasdeveloped and compared with conventional methods in nine mongrel dogs.MRIs were obtained covering the entire lungs. Injury was induced byinjection of oleic acid (0.021-0.048 ml/kg) into a jugularcatheter. Imaging followed for 0.75-2 h. Extravascular lung waterand permeability-related parameters were measured from multiple-indicator dilution curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR). Postinjury wet-to-dry lung weight ratio was 5.30 ± 0.38 (n = 9). Extravascular lung water increased from 2.03 ± 1.11 to 3.00 ± 1.45 ml/g(n = 9, P < 0.01). Indicatordilution studies yielded parameters characterizing capillary exchangeof urea and butanediol: the product of the square root of equivalentdiffusivity of escape from the capillary and capillary surface area(D^1/2S)and the capillary permeability-surface area product(PS). The ratio ofD^1/2Sfor urea toD^1/2Sfor butanediol increased from 0.583 ± 0.027 to 0.852 ± 0.154 (n = 9, P < 0.05). Whole lung SNR atbaseline, before injury, correlated withD^1/2Sand PS ratios (both P < 0.02). By using rate of SNR change, the mismatch of transcapillaryfiltration flow and lymph clearance was estimated to be0.2-1.8 ml/min. The filtration coefficient was estimated fromthese values. Results indicate that pulmonary edema formation duringoleic acid injury can be imaged regionally and quantified globally, andthe results suggest possible regional quantification by usingthree-dimensional MRI.

     

Mechanism of Photoregulated Carotenogenesis in Rhodotorula minuta II. Aspects of Photoregulative Reaction

The photoregulation of carotenogenesis in Rhodotorula minutawas found to consist of tow phases, a temperature-independentphotochemical reaction (light process) and temperature-dependentbut light-independent biochemical reactions (dark process).These processes were separately examined by regulating the temperatureand were characterized as follows: 1) The quantity of carotenoid produced [C (µg g^–1)]and the rate of carotenoid production [Vc (µg g^–1hr^–1)] in the dark process were regulated by the lightdose [D (erg cm^–2)] to which cells were exposed in thelight process. These relationships were expressed by the equations:C=9.1 log D–62.0 and Vc=0.81 log D–5.60. This photoresponsefollowed the Roscoe-Bunsen reciprocity law. 2) The induced state toward carotenogenesis, once acquired inthe light process, was very stable, suggesting that the proposedphotochemical product is stable as an inducer of carotenogenesisand decreases only in conjunction with carotenoid biosynthesis. 3) The photochemical reaction was oxygen-independent, but subsequentdark reactions were completely dependent on oxygen. 4) Postulated compounds related to the photochemical reactionwere not metabolized in vivo. (Received September 12, 1981; Accepted February 20, 1982)     

Effect of concentration on albumin diffusion in lung interstitium

The transport of macromolecules through the lung interstitiumdepends on both bulk transport of fluid and diffusion. In the presentstudy, we studied the diffusion of albumin. Isolated rabbit lungs wereinflated with silicon rubber via airways and blood vessels, and twochambers were bonded to the sides of a 0.5-cm-thick slab that encloseda vessel with an intersititial cuff. One chamber was filled with eitheralbumin solution (2 or 5 g/dl) containing tracer¹²⁵I-albumin or with tracer¹²⁵I-albumin alone; the other wasfilled with Ringer solution. Unbound ¹²⁵I was removed from the tracerby dialysis before use. The chamber with Ringer solution was placed inthe well of a NaI(Tl) scintillation detector. Diffusion oftracer through the interstitium was measured continuously for 60 h.Tracer mass (M) showed a time(t) delay followed by an increase toa steady-state flow(dM/dtconstant). Albumin diffusion coefficient(D) was given byL²/(6T),where T was the time intercept of thesteady-stateM-t line at zero M, andL was interstitial length.Interstitial cuff thickness-to-vessel radius ratio(Th₀/R)was estimated by using Fick's law for steady-state diffusion. BothD andTh₀/Rwere independent of albumin concentration.D averaged 6.6 × 10⁷cm²/s, similar to the freeD for albumin. Values ofTh₀/Raveraged 0.047 ± 0.024 (SD), near the values measuredhistologically. Thus pulmonary interstitial constituents offered norestriction to the diffusion of albumin.

     

HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat

High mobility group box 1 (HMGB1) acts as an early mediator in inflammation and organ injury. Ischemia reperfusion (I/R) injury induces HMGB1 translocation and expression in ischemic areas. However, it is unknown whether selective warm liver I/R injury also induces the expression of HMGB1 in non-ischemic lobes. The present study aimed to test the hypothesis that selective liver I/R injury also causes HMGB1 translocation and up-regulates its expression in non-ischemic liver areas. In the present study, selective I/R injury was induced by clamping the median and left lateral liver lobes for 90 min followed by 0.5, 6 and 24 h reperfusion. We used male inbred Lewis rats; six animals for each point in time and six animals for the normal control group. Selective hepatic I/R injury induced morphological changes not only in ischemic lobes but also in non-ischemic lobes. HMGB1 translocation and expression was increased in a time-dependent manner in the ischemic lobes, and increased in with delayed onset in the non-ischemic lobes. Serum HMGB1 levels were increased after reperfusion. Furthermore, liver I/R injury up-regulated the expression of HMGB1 receptors (Toll-like receptor 4 and receptor for advanced glycation end products and pro-inflammatory cytokines (Tumor necrosis factor-alpha and interleukin-6) in both ischemic lobes, however, the up-regulation of these cytokines was more prominent in the ischemic lobes. In conclusion, selective warm I/R induces a substantial “sympathetic/bystander” effect on the non-ischemic lobes in terms of HMGB1 translocation and local cytokine production.     

Luminal L-alanine stimulates exocytosis at the K+-conductive apical membrane of Aplysia enterocytes

In Aplysia intestine,stimulation of Na⁺ absorption withluminal alanine increases apical membraneK⁺ conductance(G_K,a), whichpresumably regulates enterocyte volume during stimulatedNa⁺ absorption. However, themechanism responsible for the sustained increase in plasma membraneK⁺ conductance is not known forany nutrient-absorbing epithelium. In the present study, we have begunto test the hypothesis that the alanine-induced increase inG_K,a inAplysia enterocytes results fromexocytic insertion of K⁺ channelsinto the apical membrane. We used the fluid-phase marker horseradishperoxidase to assess the effect of alanine on apical membraneexocytosis and conventional microelectrode techniques to assess theeffect of alanine on fractional capacitance of the apical membrane(fC_a). Luminalalanine significantly increased apical membrane exocytosis from 1.04 ± 0.30 to 1.39 ± 0.38 ng · min¹ · cm².To measure fC_a,we modeled the Aplysia enterocyte as adouble resistance-capacitance (RC) electric circuit arranged in series. Several criteria were tested to confirm application of the model to theenterocytes, and all satisfied the model. When added to the luminalsurface, alanine significantly increasedfC_a from 0.27 ± 0.02 to 0.33 ± 0.04 (n = 10)after 4 min. There are two possible explanations for our findings:1) the increase in exocytosis, whichadds membrane to the apical plasma membrane, prevents plasma membranefracture, and 2) the increase inexocytosis delivers K⁺ channels tothe apical membrane by exocytic insertion. After the alanine-induceddepolarization of apical membrane potential (V_a), there isa strong correlation (r = 0.96)between repolarization ofV_a, whichreflects the increase inG_K,a, andincrease in fC_a. This correlation supports the exocytic insertion hypothesis for activation ofG_K,a.

     

Shear stress induces a time- and position-dependent increase in endothelial cell membrane fluidity

Blood flow-associatedshear stress may modulate cellular processes through its action on theplasma membrane. We quantified the spatial and temporal aspects of theeffects of shear stress () on the lipid fluidity of1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiIC₁₆(13)]-stained plasma membranesof bovine aortic endothelial cells in a flow chamber. A confocalmicroscope was used to determine the DiI diffusion coefficient(D) by fluorescence recovery after photobleaching on cellsunder static conditions, after a step- of 10 or 20 dyn/cm², and after the cessation of . The methodallowed the measurements of D on the upstream and downstreamsides of the cell taken midway between the respective cell borders andthe nucleus. In <10 s after a step- of 10 dyn/cm²,D showed an upstream increase and a downstream decrease, and both changes disappeared rapidly. There was a secondary, larger increase in upstream D, which reached a peak at 7 min and decreased thereafter, despite the maintenance of .D returned to near control values within 5 s aftercessation of . Downstream D showed little secondarychanges throughout the 10-min shearing, as well as after its cessation.Further investigations into the early phase, with simultaneousmeasurements of upstream and downstream D, confirmed that astep- of 10 dyn/cm² elicited a rapid (5-s) but transientincrease in upstream D and a concurrent decrease indownstream D, yielding a significant difference between thetwo sites. A step- of 20 dyn/cm² caused D toincrease at both sites at 5 s, but by 30 s and 1 min theupstream D became significantly higher than the downstream D. These results demonstrate shear-induced changes inmembrane fluidity that are time dependent and spatially heterogeneous. These changes in membrane fluidity may have important implications inshear-induced membrane protein modulation.

     

K+ transport and capacitance of the basolateral membrane of the larval frog skin

Skin from larval bullfrogs was mounted in an Ussing-type chamberin which the apical surface was bathed with a Ringer solution containing 115 mM K⁺ and thebasolateral surface was bathed with a Ringer solution containing 115 mMNa⁺. Ion transport was measured asthe short-circuit current(I_sc) with alow-noise voltage clamp, and skin resistance(R_m) wasmeasured by applying a direct current voltage pulse. Membrane impedance was calculated by applying a voltage signal consisting of 53 sine wavesto the command stage of the voltage clamp. From the ratio of theFourier-transformed voltage and current signals, it was possible tocalculate the resistance and capacitance of the apical and basolateralmembranes of the epithelium(R_a andR_b,C_a and C_b,respectively). With as the anion,R_m decreasedrapidly within 5 min following the addition of 150 U/ml nystatin to theapical solution, whereasI_sc increasedfrom 0.66 to 52.03 µA/cm² over a60-min period. These results indicate that nystatin becomes rapidlyincorporated into the apical membrane and that the increase inbasolateral K⁺ permeabilityrequires a more prolonged time course. Intermediate levels ofI_sc were obtainedby adding 50, 100, and 150 U/ml nystatin to the apical solution. Thisproduced a progressive decrease in R_a andR_b whileC_a andC_b remainedconstant. With Cl as theanion, I_sc valuesincreased from 2.03 to 89.57 µA/cm² following treatment with150 U/ml nystatin, whereas with gluconate as the anionI_sc was onlyincreased from 0.63 to 11.64 µA/cm². This suggests that theincrease in basolateral K⁺permeability produced by nystatin treatment, in the presence of morepermeable anions, is due to swelling of the epithelial cells of thetissue rather than the gradient for apicalK⁺ entry. Finally,C_b was notdifferent among skins exposed toCl,, or gluconate, despite the largedifferences inI_sc, nor didinhibition of I_scby treatment with hyperosmotic dextrose cause significant changes inC_b. These resultssupport the hypothesis that increases in cell volume activateK⁺ channels that are alreadypresent in the basolateral membrane of epithelial cells.

     

Effect of IBMX and alkaline phosphatase inhibitors on Cl- secretion in G551D cystic fibrosis mutant mice

Some cysticfibrosis transmembrane conductance regulator (CFTR) mutations, such asG551D, result in a correctly localized Cl channel at the cellapical membrane, albeit with markedly reduced function. Patch-clampstudies have indicated that both phosphatase inhibitors and3-isobutyl-1-methylxanthine (IBMX) can induceCl secretion through theG551D mutant protein. We have now assessed whether these agents caninduce Cl secretion incftr^G551D mutantmice. No induction of Clsecretion was seen with the alkaline phosphatase inhibitorsbromotetramisole or levamisole in either the respiratory or intestinaltracts of wild-type orcftr^G551D mice.In contrast, in G551D intestinal tissues, IBMX was able to produce asmall CFTR-related secretory response [means ± SE: jejunum,1.8 ± 0.9 µA/cm²,n = 7; cecum, 3.7 ± 0.8 µA/cm²,n = 7; rectum (in vivo),1.9 ± 0.9 mV, n = 5]. Thiswas approximately one order of magnitude less than the wild-typeresponse to this agent and, in the cecum, was significantly greaterthan that seen in null mice(cftr^UNC). Inthe trachea, IBMX produced a transientCl secretory response (37.3 ± 14.7 µA/cm²,n = 6) of a magnitude similar to thatseen in wild-type mice (33.7 ± 4.7 µA/cm²,n = 9). This response was also presentin null mice and therefore is likely to be independent of CFTR. Noeffect of IBMX on Clsecretion was seen in the nasal epithelium ofcftr^G551D mice.We conclude that IBMX is able to induce detectable levels ofCFTR-related Cl secretionin the intestinal tract but not the respiratory tract through the G551Dmutant protein.

     

Mechanism of mosaic attenuation of the lungs on computed tomography in induced bronchospasm

The purpose of this study was to investigatewhether hypoxic pulmonary vasoconstriction is the major determinant ofthe computed tomography (CT) pattern of mosaic attenuation in asthmaticpatients with induced bronchoconstriction. Thin-section CT wasperformed at suspended full inspiration immediately and 30 min aftermethacholine bronchoprovocation in 22 asthmatic subjects, who wererandomly assigned to breathe room air (group A,n = 8), oxygen via nasal prongs at 5 l/min (group B,n = 8), and oxygen via face mask at 12 l/min (group C,n = 6). CT changes were quantified interms of global lung density and density in hypodense and hyperdense areas. Lung parenchymal density increases were greatest ingroup C and greater ingroup B than in groupA, globally (P = 0.03) and in hypodense regions (P = 0.01).On bivariate analysis, the only change in cross-sectional area wasrelated to change in global density. In hypodense regions, densitychange was related both to reduction in cross-sectional area(P < 0.0005) and to oxygen administration (P = 0.01). Aftercorrection for changes in global lung density, only oxygen wasindependently related to density increase in hypodense areas(P = 0.02). In inducedbronchoconstriction, the CT appearance of mosaic attenuation can belargely ascribed to hypoxic vasoconstriction rather than to changes inlung inflation.     

Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100km

Madsen, Klavs, Dave A. MacLean, Bente Kiens, and DirkChristensen. Effects of glucose, glucose plus branched-chain aminoacids, or placebo on bike performance over 100 km. J. Appl. Physiol. 81(6): 2644-2650, 1996.This studywas undertaken to determine the effects of ingesting either glucose(trial G) or glucose plusbranched-chain amino acids (BCAA; trialB), compared with placebo (trialP), during prolonged exercise. Nine well-trained cyclists with a maximal oxygen uptake of 63.1 ± 1.5 mlO₂ ^· min^{1 ·} kg¹performed three laboratory trials consisting of 100 km of cycling separated by 7 days between each trial. During these trials, the subjects were encouraged to complete the 100 km as fast as possible ontheir own bicycles connected to a magnetic brake. No differences inperformance times were observed between the three trials (160.1 ± 4.1, 157.2 ± 4.5, and 159.8 ± 3.7 min, respectively). Intrial B, plasma BCAA levels increased from339 ± 28 µM at rest to 1,026 ± 62 µM after exercise(P < 0.01). Plasma ammoniaconcentrations increased during the entire exercise period for allthree trials and were significantly higher intrial B compared withtrials G andP (P < 0.05). The respiratory exchange ratio was similar in the threetrials during the first 90 min of exercise; thereafter, it tended todrop more in trial P than intrials G andB. These data suggest that neitherglucose nor glucose plus BCAA ingestion during 100 km of cyclingenhance performance in well-trained cyclists.

     

Nonlinear systems identification: autocorrelation vs. autoskewness

Sammon, Michel, and Frederick Curley. Nonlinear systemsidentification: autocorrelation vs. autoskewness. J. Appl. Physiol. 83(3): 975-993, 1997.Autocorrelation function(C¹) orautoregressive model parameters are often estimated for temporal analysis of physiological measurements. However, statisticalapproximations truncated at linear terms are unlikely to be ofsufficient accuracy for patients whose homeostatic control systemscannot be presumed to be stable local to a single equilibrium. Thus aquadratic variant ofC¹[autoskewness function(C²)] isintroduced to detect nonlinearities in an output signal as a functionof time delays. By use of simulations of nonlinear autoregressivemodels, C² isshown to identify only those nonlinearities that "break" the symmetry of a system, altering the mean and skewness of its outputs. Case studies of patients with cardiopulmonary dysfunction demonstrate arange of ventilatory patterns seen in the clinical environment; whereastesting of C¹reveals their breath-by-breath minute ventilation to be significantly autocorrelated, theC² test concludesthat the correlation is nonlinear and asymmetrically distributed.Higher-order functionals [e.g., autokurtosis(C³)] arenecessary for global analysis of metastable systems that continuously"switch" between multiple equilibrium states and unstable systemsexhibiting nonequilibrium dynamics.

     

Changes in intracellular Ca2+ concentration induced by L-type Ca2+ channel current in guinea pig gastric myocytes

We investigatedthe relationship between voltage-operatedCa²⁺ channel current and thecorresponding intracellular Ca²⁺concentration([Ca²⁺]_i)change (Ca²⁺ transient) in guineapig gastric myocytes. Fluorescence microspectroscopy was combined withconventional whole cell patch-clamp technique, and fura 2 (80 µM) wasadded to CsCl-rich pipette solution. Step depolarization to 0 mVinduced inward Ca²⁺ current(I_Ca) andconcomitantly raised[Ca²⁺]_i.Both responses were suppressed by nicardipine, an L-typeCa²⁺ channel blocker, and thevoltage dependence of Ca²⁺transient was similar to the current-voltage relation ofI_Ca. When pulseduration was increased by up to 900 ms, peakCa²⁺ transient increased andreached a steady state when stimulation was for longer. The calculatedfast Ca²⁺ buffering capacity(B value), determined as the ratio ofthe time integral ofI_Ca divided bythe amplitude of Ca²⁺ transient,was not significantly increased after depletion of Ca²⁺ stores by the cyclicapplication of caffeine (10 mM) in the presence of ryanodine (4 µM).The addition of cyclopiazonic acid (CPA, 10 µM), a sarco(endo)plasmicreticulum Ca²⁺-ATPase inhibitor,decreased B value by ~20% in areversible manner. When KCl pipette solution was used,Ca²⁺-activatedK⁺ current[I_K(Ca)]was also recorded during step depolarization. CPA sensitivelysuppressed the initial peak and oscillations of I_K(Ca) withirregular effects on Ca²⁺transients. The above results suggest that, in guinea pig gastric myocyte, Ca²⁺ transient is tightlycoupled to I_Caduring depolarization, and global[Ca²⁺]_iis not significantly affected byCa²⁺-inducedCa²⁺ release from sarcoplasmicreticulum during depolarization.

     

Hypoxia- and normoxia-induced reversibility of autonomic control in Andean guinea pig heart

León-Velarde, Fabiola, Jean-Paul Richalet, Juan-CarlosChavez, Rachid Kacimi, Maria Rivera-Chira, José-Antonio Palacios, and Daniel Clark. Hypoxia- and normoxia-induced reversibility ofautonomic control in Andean guinea pig heart. J. Appl.Physiol. 81(5): 2229-2234, 1996.We hereindescribe the regulation of cardiac receptors in a typical high-altitudenative animal. Heart rate response to isoproterenol(HR_Iso)(beats ^· min^{1 ·} mgIso ^· kg¹)and atropine, the density of -adrenergic(_AR) and muscarinic (M₂) receptors, and theventricular content of norepinephrine (NE) and dopamine (DA) werestudied in guinea pigs (Caviaporcellus). Animals native to Lima, Peru (150 m) werestudied at sea level (SL) and after 5 wk at 4,300-m altitude (SL-HA).Animals native to Rancas [Pasco, Peru (4,300 m)] werestudied at high altitude (HA) and after 5 wk at SL (HA-SL). HA animalshad a lower HR_Iso, maximum numberof _AR binding sites(B_max),_AR dissociation constant (K_d), NE, andDA (P < 0.05) and a higherM₂B_max(P < 0.001) when compared with theSL group. HA-SL showed an increase of theHR_Iso, _ARK_d, and NE(P < 0.05) and a decrease of theM₂B_max andK_d (P < 0.0001) when compared with theHA group. The present study demonstrates the differential regulationand reversibility of the autonomic control in the guinea pig heart.

     

Irradiance and daylength effects on growth and chemical composition of Gyrodinium aureolum Hulburt in culture

For Gyrodinium aureolum significant irradiance and daylengtheffects were found on the division rate and on the growth-relevantChla-normalized photosynthetic rate (^gP^B). Optimum conditionsof irradiance and daylength were found at 230 µmol m^–2s^–1 and 14 h for the division rate, and at >260 µmolm^–2 s^–1 and <6 h for ^gP^B.^gP^B showed no photoinhibition,while the division rate decreased markedly at irradiances abovesaturation. This difference and the difference in optimum irradiancebetween the division rate and ^gP^B are explained by a decreasein cellular Chla/carbon ratio with increasing irradiance. Thecellular content of carbon and nitrogen decreased significantlywith increasing irradiance. Total phosphorus was independentof irradiance and daylength. Below the saturation irradiancefor ^gP^B the daily Chla-normalized carbon yield may be describedas an exponential function of the daily irradiance (irradiancex daylength).     

Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors

Dupuis, Jocelyn, Carl A. Goresky, and Alain Fournier.Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ET_B receptors.J. Appl. Physiol. 81(4):1510-1515, 1996.The pulmonary circulation plays an importantrole in the removal of circulating endothelin-1 (ET-1). Plasma ET-1levels are increased in pulmonary hypertensive states of variousetiologies (e.g., idiopathic, heart failure, and congenital anomalies)in proportion to the severity of pulmonary hypertension. It is possible that reduced pulmonary clearance of this peptide contributes to thehyperendothelinemia of those pathologies. TheET_A andET_B receptors are abundant in lungtissues: on the vascular endothelium, theET_B receptor is predominant andmay contribute to ET-1 extraction through receptor-mediatedendocytosis. We designed experiments to determine and quantify theimportance of the ET_A andET_B receptors in the pulmonaryextraction of circulating ET-1 in anesthetized dogs. The single-passcumulative tracer ET-1 extraction by the lung was measured with theindicator-dilution technique before and 5 min after intrapulmonaryinjection of the specific ET_Aantagonist BQ-123 (n = 5, 120-960nmol) and the specific ET_Bantagonist BQ-788 (n = 6, 1,000 nmol).The inhibitors had no significant effect on pulmonary and systemichemodynamics. Mean cumulative pulmonary ET-1 extraction was notmodified by BQ-123 [control (C): 36 ± 4%, antagonist (A): 34 ± 6%] but was completely abolished by BQ-788 (C: 34 ± 6%, A: 0 ± 2%, P < 0.001). Thepulmonary rate constant (K) for ET-1removal was also unaffected by BQ-123 (C: 0.050 ± 0.0085 s¹, A: 0.047 ± 0.012 s¹) but significantlydecreased and became close to zero after BQ-788 (C: 0.058 ± 0.014 s¹, A: 0.009 ± 0.007 s¹,P < 0.001). We conclude that theET_B receptor is completely andexclusively responsible for pulmonary ET-1 removal in vivo. Futurestudies are needed to show whether desensitization or downregulation ofthe ET_B receptor may contribute tothe increase in circulating ET-1 levels in conditions associated withpulmonary hypertension. This novel pulmonary endothelial cell functionmay play a protective role by modulating circulating ET-1 levels in thesystemic circulation.

     

Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain

Brain hypoxiainduces an increase in brain vascularity, presumably mediated byvascular endothelial growth factor (VEGF), but it is unclear whetherVEGF is required to maintain the increase. In these studies, brain VEGFmRNA and protein levels were measured in adult mice kept in hypobaricchambers at 0.5 atm for 0, 0.5, 1, 2, 4, 7, and 21 days. Hypoxia wasaccompanied by a transient increase of VEGF mRNA expression: twofold by0.5 day and a maximum of fivefold by 2 days; these were followed by adecrease at 4 days and a return to basal levels by 7-21 days. VEGFprotein expression induced by hypoxia was bimodal, initiallyparalleling VEGF mRNA. There was an initial small increase at 12 h thatreached a maximum by day 2, and, aftera transient decrease on day 4, theprotein expression increased again on day7 before it returned to normoxic levels after 21 days.Thus, despite continued hypoxia, both VEGF mRNA and protein levelsreturned to basal after 7 days. These data suggest a metabolicnegative-feedback system for VEGF expression during prolonged hypoxiain the brain.