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The American journal of physiology.
Publisher:
American Physiological Society.. Bethesda, MD : American Physiological Society
Frequency: Monthly
Country: United States
Language: English
Author(s):
American Physiological Society (1887- ), American Physiological Society (1887- )., American Physiological Society (1887- ).
Start Year:1898 -
Identifiers
| ISSN: | 0002-9513 (Print) 2163-5773 (Electronic) 0002-9513 (Linking) |
| NLM ID: | 0370511 |
| (OCoLC): | 01480180 |
| (DNLM): | A24720000(s) |
| Coden: | AJPHAP |
| LCCN: | a 43003158 |
| Classification: | W1 AM507 |
A selective increase in circulating inhibin and inhibin pro-alphaC at the time of ovulation in the mare. The relationship between a selective increase in circulating immunoreactive (ir)-inhibin and the time of ovulation was investigated in mares. Concentrations of plasma ir-inhibin were measured every 4 h during the periovulatory period. Inhibin pro-alphaC, a precursor protein of the inhibin alpha-subunit, was also measured. The changes in ir-inhibin and inhibin pro-alphaC in circulation were parallel. Concentrations of both ir-inhibin and inhibin pro-alphaC in the plasma increased at the same time when ovulatory follicles ruptured, and the peak levels of circulating ir-inhibin and inhibin pro-al...
Pre- and postjunctional effects of inflammatory mediators in horse airways. In addition to their direct contractile effects, histamine (Hist), serotonin [5-hydroxytryptamine (5-HT)], and leukotriene (LT) D(4), in low concentrations, dramatically augment electrical field stimulation (EFS)-induced smooth muscle contractions in equine airways. To determine the mechanism of their action, we studied, in trachealis strips, the effect of these mediators on both cholinergically induced tension and the release of ACh from cholinergic nerves. All three mediators synergistically augmented the contraction of the trachealis that was due to release of endogenous ACh, i.e., EFS-indu...
Modulation of ACh release from airway cholinergic nerves in horses with recurrent airway obstruction. To evaluate the functional status of neuronal alpha2-adrenoceptors (ARs) and beta2-ARs on ACh release in horses with recurrent airway obstruction (RAO), we examined the effects of the physiological agonists epinephrine (Epi) and norepinephrine (NE) and the beta2-agonists RR- and RR/SS-formoterol on ACh release from airway cholinergic nerves of horses with RAO. Because SS-formoterol, a distomer of the beta2-agonist, increases ACh release from airways of control horses only after the autoinhibitory muscarinic receptors are blocked by atropine, we also tested the hypothesis that if there is an M2...
Mediators of anaphylaxis but not activated neutrophils augment cholinergic responses of equine small airways. Neutrophilic inflammation in small airways (SA) and bronchospasm mediated via muscarinic receptors are features of chronic obstructive pulmonary disease in horses (COPD). Histamine, serotonin, and leukotrienes (LTs) are reported to be involved in the exacerbation of COPD, and currently, histamine has been shown to increase tension response to electrical field simulation (EFS) in equine SA. We tested the effects of these mediators and the effects of activated neutrophils on the cholinergic responses in SA. Histamine, serotonin, and LTD4 had a synergistic effect on EFS responses and only an addi...
Effects of local anesthetics on Na+ channels containing the equine hyperkalemic periodic paralysis mutation. We examined the ability of local anesthetics to correct altered inactivation properties of rat skeletal muscle Na+ channels containing the equine hyperkalemic periodic paralysis (eqHPP) mutation when expressed in Xenopus oocytes. Increased time constants of current decay in eqHPP channels compared with wild-type channels were restored by 1 mM benzocaine but were not altered by lidocaine or mexiletine. Inactivation curves, which were determined by measuring the dependence of the relative peak current amplitude after depolarization to -10 mV on conditioning prepulse voltages, could be shifted in...
Role of cAMP and neuronal K+ channels on alpha 2-AR-induced inhibition of ACh release in equine trachea. To investigate the effects of changes in intracellular cAMP on alpha 2-adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we examined the effects of the alpha 2-AR agonist clonidine on electrical field stimulation-evoked ACh release from equine tracheal parasympathetic nerves before and after treatment with 8-bromo-cAMP or forskolin. We also tested whether charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca(2+)-activated K+ channels mediate alpha 2-AR-induced inhibition by examining the effect of clonidine in the absence and presence of ChTX or IBTX on ACh release...
Interindividual variation in total and carrier-mediated lactate influx into red blood cells. To study in standardbred horses interindividual variation in the influx of lactate into red blood cells, venous blood samples were collected from 89 horses from 2 wk to 9 yr of age. For 62 horses, the rate of influx was normally distributed with a mean rate of 4.09 nmol.mg protein-1.min-1 at a lactate concentration of 10 mM, and the respective value for the other 27 horses was 0.58 nmol.mg protein-1.min-1. At 30 mM of lactate, the rates were 8.71 and 1.97 nmol.mg protein-1.min-1, respectively. This bimodal distribution was independent of age. In horses with high transport activity, the monocar...
Effects of enantiomers of beta 2-agonists on ACh release and smooth muscle contraction in the trachea. The beta 2-agonists currently used as bronchodilators are racemic mixtures of R- and S-enantiomers. In the present study, we examined the effects of enantiomers of the beta 2-agonists albuterol and formoterol on acetylcholine (ACh) release from equine trachealis parasympathetic nerves. ACh release was evoked by electrical field stimulation (20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography coupled with electrochemical detection. We also tested the effects of enantiomers of albuterol and formoterol on equine tracheal smooth muscle (TSM) contraction in response to exog...
Erythrocyte aggregation tendency and cellular properties in horse, human, and rat: a comparative study. Horse blood has a higher tendency to form red blood cell (RBC) aggregates compared with human blood, with this enhanced aggregation previously attributed to differences in plasma factors. Our results confirm this observation and further indicate that washed horse RBC also have a significantly higher aggregation tendency in dextran 70 solutions (i.e., horse RBC have a higher "aggregability"). In contrast, the aggregation tendency of rat RBC, both in autologous plasma and in dextran 70, is significantly less compared with human and horse RBC. Other rheological findings for horse and rat RBC incl...
Effect of changes in respiratory blood parameters on equine red blood cell K-Cl cotransporter. K influx into equine red blood cells (RBCs) was measured using 86Rb as a tracer for K under conditions designed to mimic the changes in respiratory blood parameters that occur in vivo during strenuous exercise. The effects on K influx of physiological changes in pH, cell volume, O2 tension (PO2), CO2 tension (PCO2), and bicarbonate and lactate concentrations were defined. Physiological PO2 exerted a dominant controlling influence on the H(+)-stimulated Cl-dependent K influx, consistent with effects on the K-Cl cotransporter, PO2 required for half-maximal activity was 37 +/- 3 mmHg (4.9 kPa). A...
Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle. The effects of capsaicin and neuropeptides were examined in equine tracheal smooth muscle (TSM). Neither capsaicin nor substance P (SP) contracted TSM. Capsaicin (100 microM) elicited relaxation in TSM contracted with methacholine. This relaxation was not mimicked by SP or calcitonin gene-related peptide (CGRP). Relaxation was not attenuated by removal of the epithelium or by pretreatment of tissue with meclofenamate or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine. Previous exposure of TSM to capsaicin did not eliminate the relaxation responses to subsequent capsaicin. Although...
Muscarinic signaling pathway for calcium release and calcium-activated chloride current in smooth muscle. We investigated the muscarinic activation of Ca(2+)-activated Cl- currents [ICl(Ca)] in voltage-clamped equine tracheal myocytes. The threshold of cytosolic free Ca2+ concentration ([Ca2+]i) required for activation of ICl(Ca) was 202 +/- 22 nM, and full activation of the current occurred at 771 +/- 31 nM. Hexahydro-sila-difenidol (M3 antagonist) inhibited the methacholine-induced phasic [Ca2+]i increase and ICl(Ca) in a concentration-dependent manner, whereas methoctramine (M2 antagonist) only slightly attenuated the [Ca2+]i increase and ICl(Ca) (14.8 and 21.4%, respectively), consistent with ...
Myoglobin content and oxygen diffusion: model analysis of horse and steer muscle. We test the hypothesis that myoglobin is important for O2 supply near the oxidative capacity of muscle. This hypothesis is evaluated with a simple model that incorporates the properties of heart and skeletal muscle tissue taken from steers and horses exercising at their maximum O2 consumption rate. These tissue samples allowed us to set the bounds on oxidative demand and O2 flux from red blood cells to the core of the muscle fiber, to estimate the blood and tissue capacities for O2 diffusion, and to define the capillary blood PO2 driving this O2 flux. A model combining blood convection with ti...
Theoretical predictions of end-capillary PO2 in muscles of athletic and nonathletic animals at VO2max. Characterizing the resistances to O2 transport from the erythrocyte to the mitochondrion is important in understanding potential transport limitations. A steady-state model of this process was developed to predict the minimum (critical) end-capillary PO2 required to prevent hypoxia at maximal O2 consumption (VO2max) in a circular region of tissue surrounding the venular end of a capillary. Capillary density was used as a measure of O2 delivery, and mitochondrial density was used as a measure of O2 consumption. The effects of oxyhemoglobin dissociation kinetics and diffusion facilitation by hem...
Cortisol disposition and production rate in horses during rest and exercise. The influence of a 56-km endurance exercise on cortisol kinetics and production rate was evaluated in six horses administered [3H]cortisol. Exercise resulted in an immediate two- to threefold increase in plasma cortisol, with values returning very rapidly to preexercise levels. During exercise, clearance and steady-state volume of distribution of total cortisol were greatly increased (338 +/- 95 vs. 137 +/- 34 ml.kg-1.h-1 for clearance and 359 +/- 82 vs. 229 +/- 18 ml/kg for volume of distribution), whereas the terminal half-life decreased significantly (0.97 +/- 0.16 vs. 1.55 +/- 0.33 h). The...
Equine coronary hemodynamics during brief coronary occlusions at three levels of collateral function. Adult-grade ponies were surgically instrumented with a Doppler flow probe and pneumatic cuff occluder on the left anterior descending coronary artery (LAD), sonomicrometry crystals and intraventricular micromanometer in the left ventricle, and catheters in the left atrium, anterior interventricular vein, and, in some animals, the LAD. Conscious-animal studies were begun 2 wk after surgery. Measured variables included regional left ventricular systolic function, end-diastolic wall thickness, oxygen extraction, lactate extraction, and hydrogen ion release. Changes in collateral perfusion were de...
Potentiation of acetylcholine release from tracheal parasympathetic nerves by cAMP. We tested the hypothesis that increasing intracellular levels of adenosine 3', 5'-cyclic monophosphate (cAMP) increases acetylcholine (ACh) release from airway parasympathetic nerves. Muscle strips from equine trachea were preincubated for 60 min with 10(-7)M atropine, 10(-6)M neostigmine, and 10(-5) M guanethidine. The ACh release was evoked by electrical field stimulation (EFS, 20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography with electrochemical detection. Agents known to increase cAMP, i.e., forskolin (10(-6) - 10(-4) M), 8-bromoadenosine 3', 5'-cyclic monophosp...
Glucose and oxygen metabolism in the fetal foal during late gestation. With the use of [U-14C]glucose tracer methodology, the rates of umbilical uptake, utilization, oxidation, and production of glucose were determined in nine chronically catheterized fetal foals in the fed state between 268 and 325 days of gestation (term approximately 335 days). At the same time, the rates of umbilical O2 and lactate uptake were measured in all nine fetuses by Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization, and CO2 production from glucose carbon were 36.9 +/- 2.5, 36.4 +/- 1.7, and 117.7 +/- 17.4 mumol.min-1.kg fetal body wt-1, respectivel...
Causes of differences in respiration rate of hepatocytes from mammals of different body mass. Resting O2 consumption of hepatocytes isolated from mammals ranging in mass from 20-g mice to 200-kg horses decreases with increasing body mass. The substrate oxidation system increases in activity with increasing body mass and mitochondrial proton leak and phosphorylation system decrease in activity, resulting in a higher mitochondrial membrane potential in hepatocytes from larger mammals. The absolute rates of O2 consumption due to nonmitochondrial processes, substrate oxidation, mitochondrial proton leak, and the phosphorylation system decrease with increasing body mass. These decreases are...
Equine pelvic flexure myoelectric activity during fed and fasted states. The pelvic flexure is the midpoint of the equine large colon that marks the junction of dorsal and ventral components. Previous studies of intraluminal pressure in this region indicate that it could be an important motility control center. The present study was undertaken to expand our knowledge of normal myoelectric activity around the pelvic flexure region. Eight bipolar silver wire electrodes were surgically fixed at 5-cm intervals to the colonic serosa of five adult horses, starting 30 cm oral to the pelvic flexure on the left ventral colon and ending 15 cm aboral to the pelvic flexure on ...
Kinetic studies and production rate of melatonin in pony mares. The aims of the present study were to determine basic kinetic parameters and the nycthemeral production rate of melatonin in the horse. Seven pony mares were used for the kinetic studies. Five other pony mares were used under long and short days for the production rate studies. Melatonin was administered by intravenous, oral, and intragastric routes at different dose levels. The plasma melatonin clearance was 1.02 +/- 0.31 l.kg-1.h-1, and the volume of distribution was 0.89 +/- 0.53 l/kg for the 0.4 microgram/kg melatonin dose. The systemic availability after oral and intragastric administrati...
Lactate influx into red blood cells of athletic and nonathletic species. Transport of lactate across the erythrocyte membrane proceeds by three distinct pathways: 1) nonionic diffusion of lactic acid, 2) inorganic anion exchange (band 3), and 3) a monocarboxylate-specific (MC) carrier mechanism. This study determined the contributions of these three pathways in the red blood cells (RBCs) of "athletic" and "nonathletic" species. Blood samples were obtained from four male animals of each species: 1) Canis familiaris (dogs), 2) Capra hircus (goats), 3) Equus caballus (horses), and 4) Bos taurus (cattle). Contribution of each pathway to total lactate influx was determi...
Catecholamine affects acetylcholine release in trachea: alpha 2-mediated inhibition and beta 2-mediated augmentation. We investigated the effects of catecholamines on acetylcholine (ACh) release from equine airway parasympathetic nerves. Trachealis strips were suspended in 2-ml tissue baths with Krebs-Henseleit solution containing atropine (10(-7) M), neostigmine (10(-6) M), and guanethidine (10(-5) M). Electrical field stimulation (20 V, 0.5 ms, 0.5 Hz, for 15 min) was applied, and ACh was measured by high-performance liquid chromatography with electrochemical detection. Epinephrine (Epi) and norepinephrine (NE) inhibited ACh release in a concentration-dependent manner. Inhibition was attenuated by the alpha...
Allometry of pharmacokinetics and pharmacodynamics of the muscle relaxant metocurine in mammals. We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmaco...
Kinetic evaluation of muscle damage during exercise by calculation of amount of creatine kinase released. To quantify the extent of muscle alteration during prolonged exercise, the release rate of creatine kinase (CK) from striated muscle was measured in six horses during a rest period (6 h) and during three exercise tests (15, 30, and 60 km) at a constant speed of 200 m/min. CK clearance was measured after intravenous bolus administration (150 U/kg) of a CK solution obtained from horse muscle. The CK steady-state volume of distribution was 0.059 +/- 0.0215 l/kg, the terminal half-life was 123 +/- 28 min, and the plasma clearance was 0.36 +/- 0.10 ml.kg-1 x min-1. After an intramuscular CK adminis...
Prejunctional alpha 2-adrenoceptors inhibit acetylcholine release from cholinergic nerves in equine airways. To determine the presence and function of alpha 2-adrenoceptors on cholinergic nerves innervating horse airway smooth muscle, the effects of some alpha 2-adrenoceptor agents on contractions of and acetylcholine (ACh) release from equine airway smooth muscle preparations were studied. Muscle contractions were elicited by either electrical field stimulation (EFS) or exogenous ACh. ACh release was induced by EFS and measured by high-pressure liquid chromatography and electrochemical detection. The alpha 2-adrenoceptor agonists clonidine (10(-7) to 10(-5) M) and UK-14,304 (10(-8) to 10(-6) M) conc...
Role of decreased plasma volume in hematocrit alterations during incremental treadmill exercise in horses. Six intact (IN) and six splenectomized (SP) mares were subjected to an incremental exercise test to examine the role of decreases in plasma volume (PV) in the changes in hematocrit (Hct) normally seen with exercise. Each horse underwent an incremental exercise test in which it ran on a treadmill up a fixed incline of 6 degrees. The test started at a speed of 4 m/s, and speed was increased 1 m/s each min until heart rate reached a plateau. Blood samples were obtained at rest and at the end of the 4, 5, 6, and 7 m/s steps of the exercise test. Resting PV was greater (P < 0.05) in the IN group...
Splenectomy alters blood pressure response to incremental treadmill exercise in horses. Six intact (IN) and five splenectomized (SP) mares were subjected to an incremental exercise test to examine the effects of splenectomy on blood pressure responses during exercise. During the test the horses ran up a 6 degree grade on a treadmill set at an initial speed of 4 m/s. Speed was increased 1 m/s every 1 min until heart rate (HR) reached a plateau. Hemodynamic data were collected continuously and analyzed for the last 18 s of the 4, 5, 6, and 7 m/s steps of the exercise test. There were no differences (P > 0.05) between the groups for resting means for any parameter measured in the...
ACh release from horse airway cholinergic nerves: effects of stimulation intensity and muscle preload. This study was conducted to determine the effects of stimulation parameters and muscle preload on acetylcholine (ACh) release induced by electrical field stimulation (EFS) of horse airway cholinergic nerves. Trachealis strip bundles were prepared and suspended in 2-ml tissue baths. The tissues were stimulated three to five times for 30 min each. Increasing frequency (0.5-16 Hz) and voltage (5-20 V) increased ACh release; increasing pulse duration (0.5-3 ms) had only a minor effect. Alterations in muscle preload (2-20 g) had no effect on ACh release. ACh release was fairly constant for up to fi...
Distribution of coronary collateral blood flow at different levels of collateral growth in conscious ponies. Coronary collateral growth was stimulated in chronically instrumented conscious ponies by a previously validated intermittent coronary occlusion method. Changes in regional myocardial function (sonomicrometry) and reactive hyperemia (Doppler method) were used to monitor collateral growth and to program measurements of regional myocardial blood flow (microsphere method). A serial analysis of the transmural and lateral distributions of collateral blood flow was performed at the native and three superimposed levels of collateral growth. Results in nine animals undergoing an average of 553 +/- 188...
