bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal sequence of endotoxin-induced systolic and diastolic myocardial depression in rabbits
Authors: Hung J. , Lew W. Y.
Published: December 2017

Twelve anesthetized rabbits received endotoxin (175 +/- 38 micrograms/kg i.v., mean +/- SD) to evaluate the temporal sequence of alterations in left ventricular (LV) function. LV volume was calculated from LV minor- and long-axis diameters, and wall thickness was measured with sonomicrometers. Hypotension, acidosis, and hypoxia were immediately corrected to eliminate these causes of myocardial depression. LV dilation developed early (1.2 +/- 0.5 h) with a significant (21 +/- 23%) increase in end-diastolic volume measured at a LV end-diastolic pressure of 5 +/- 6 mmHg. The LV stiffness did not change, and the LV dilation did not progressively worsen. Significant systolic depression developed later (2.8 +/- 1.0 h) with a 32 +/- 22% increase in end-systolic volume measured at a LV end-systolic pressure of 69 +/- 9 mmHg. The late preterminal phase (4.1 +/- 0.8 h) was characterized by a progressive increase in end-systolic volume (73 +/- 41% above control) and a significant (53 +/- 34%) increase in tau, the time constant of LV pressure fall. Diastolic abnormalities (LV dilation and increased tau) were not attributable to depressed contractility or altered hemodynamics. We conclude that endotoxin impairs systolic and diastolic LV function with distinct differences in time course. This suggests that contractility, relaxation, and passive LV properties are impaired by different endotoxin-mediated pathways and/or have different sensitivities to endotoxin.
Left ventricular energetics in closed-chest dogs
Authors: Prabhu S. D. , Freeman G. L.
Published: December 2017

Studies of ventricular energetics using the relation between myocardial O2 consumption (MVO2) and pressure-volume area (PVA) have been performed extensively in the isolated heart, but not in the intact animal. We characterized the MVO2-PVA relation and its response to heart rate (HR) in eight closed-chest dogs instrumented with high-fidelity micromanometers, piezoelectric crystals, coronary flow probes, and coronary sinus oximetric catheters. The effect of dobutamine was studied in five dogs. MVO2 is linearly related to PVA with lower MVO2 required for the generation of smaller PVAs. Baseline contractile efficiency (EFF) was 25.6 +/- 2.8%. High pacing rates reduced EFF (25.7 +/- 3.2% at a HR of 107 +/- 3 beats/min vs. 16.3 +/- 2.4% at a HR of 194 +/- 5 beats/min, P < 0.0167) and load-independent MVO2 per beat (0.562 +/- 0.119 vs. 0.377 +/- 0.074 J.beat-1 x 100 g LV-1, P < 0.0167) while increasing end-systolic elastance (Ees) (9.4 +/- 1.3 vs. 18.6 +/- 3.1 mmHg/ml, P < 0.0167). Dobutamine administration increased load-independent MVO2 per beat (0.392 +/- 0.108 vs. 0.607 +/- 0.083 J.beat-1 x 100 g LV-1, P < 0.05) and contractility (Ees 10.1 +/- 1.5 vs. 32.0 +/- 7.6 mmHg/ml, P < 0.05) without changing EFF (28.8 +/- 3.8 vs. 30.3 +/- 3.8%, P = NS). Thus the intact animal displays loss of EFF at high heart rates but maintains EFF during dobutamine stimulation. Both interventions increased load-independent MVO2 per minute, indicating increased O2 requirements for excitation-contraction coupling.
Effect of muscle length on the in vitro comparison of femoral arteries before and after endotoxin shock
Authors: Zhou Z. , Price J. M. , Sutton E. T. , Baker C. H.
Published: December 2017

Control and endotoxin-treated femoral arteries were compared in vitro for the effect of muscle length. Rats were anesthetized with pentobarbital, and endotoxin (6 mg/kg) was infused for 1 h. A control ring before endotoxin treatment and a ring after endotoxin treatment (blood pressure = 40 mmHg) were excised from the contralateral artery for length-tension and dose-response experiments with phenylephrine. The initial length for resting tension (Li) was shorter for endotoxic rings (1.23 +/- 0.01 vs. 1.41 +/- 0.02 mm in control), but the length of maximum active tension (Lmax) was the same. In length-tension experiments the values for active tension (6.36 +/- 0.61 vs. 4.06 +/- 0.60 x 10(3) dyn/cm), preload at Lmax (1,333 +/- 204 vs. 733 +/- 146 mg), and passive stiffness were increased after endotoxin. In dose-response experiments at the same preload, the endotoxic rings had a lower active tension (3.28 +/- 0.28 vs. 6.55 +/- 0.27 x 10(3) dyn/cm) but the same sensitivity. At Lmax, active tension (12.45 +/- 0.48 vs. 5.01 +/- 0.89 x 10(3) dyn/cm in control vessels) and sensitivity (half-maximum effective dose = 0.68 +/- 0.8 x 10(-6) vs. 1.39 +/- 0.29 x 10(-6) M in control vessels) were greater for endotoxic rings. These experiments show that phenylephrine sensitivity and active tension in the rat femoral artery are increased by endotoxin shock, and the importance of muscle length is implied.
Evidence for sensing and integration of biological signals by the capillary network
Authors: Song H. , Tyml K.
Published: December 2017

The aim of this study was to explore the phenomenon first described by Dietrich (Microvasc. Res. 38: 125-135, 1989) in which a local application of norepinephrine (NE) on a capillary can temporarily reduce flow via constriction of the feeding arteriole. Our objectives were to show that this phenomenon of remote response is not limited to vasoconstriction, can be elicited by materials other than NE, shows stimulus-strength dependency, and can be integrated within the capillary network. We used an intravital micropharmacological approach to iontophoretically apply (in mM concentrations in the pipette) NE, acetylcholine (ACh), 5'-N-ethylcarboxamidoadenosine (NECA, adenosine analogue), K+, and H+ on capillaries of the frog sartorius muscle in situ. Responses were measured in terms of changes in velocity of red blood cells (VRBC) in capillaries or in terms of changes in arteriolar diameter. ACh (3 mM) caused significant increases in diameter (from 34 to 37 microns) and in VRBC (from 250 to 340 microns/s, i.e., 36%). NE (3 mM) reduced VRBC by 16%. The magnitude of ACh and NE velocity responses increased with increasing pipette concentration and with increasing iontophoretic current. The ACh response was blocked by a local pretreatment with atropine. NECA, K+, and H+ caused 20-40% increases in VRBC. Dual application of NE on two capillaries fed by the same arteriole resulted in a greater VRBC reduction than for single NE application. Dual application of NE and ACh significantly attenuated the ACh response.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenoceptor mechanism involved in thiopental-epinephrine-induced arrhythmias in dogs
Authors: Hayashi Y. , Kamibayashi T. , Sumikawa K. , Yamatodani A. , Kuro M. , Yoshiya I.
Published: December 2017

The authors investigated the role of alpha 1- and beta-adrenoceptors on induction of ventricular arrhythmias during thiopental anesthesia in dogs and compared with that during halothane anesthesia. Throughout this study, arrhythmogenic threshold of epinephrine during thiopental anesthesia was designed to be comparable with that during halothane anesthesia. Phenylephrine, an alpha 1-agonist, and isoproterenol, a beta-agonist, consistently failed to provoke arrhythmias during thiopental or halothane anesthesia. The interaction between phenylephrine and isoproterenol in inducing arrhythmias was synergistic and additive during halothane and thiopental anesthesia, respectively, indicating that adrenoceptor mechanism in thiopental-epinephrine arrhythmias is different from that in halothane-epinephrine arrhythmias. During thiopental anesthesia, incidence of arrhythmias with blood pressure elevation by epinephrine, phenylephrine, or angiotensin II was not different, and increasing heart rate by electrical pacing did not replace isoproterenol in the arrhythmogenic interaction between isoproterenol and phenylephrine. The results indicate that blood pressure elevation due to the combined inotropic action of alpha 1- and beta-adrenoceptor agonists is a critical factor in the genesis of thiopental-epinephrine arrhythmias.
An optical device to measure the dynamics of apex rotation of the left ventricle
Authors: Gibbons Kroeker C. A. , Ter Keurs H. E. , Knudtson M. L. , Tyberg J. V. , Beyar R.
Published: December 2017

Systolic counterclockwise rotation of the left ventricular apex with respect to the base has been defined as left ventricular (LV) twist or torsion. If rotation of the base during systole is small, we hypothesized that the dynamics of twist can be well characterized through the measurement of apical rotation alone. A device was designed to measure apical rotation in a simpler, more direct fashion, providing continuous high-fidelity dynamic measurements. The device consists of a light source, a position-sensitive diode, and a small rotating mirror that is coupled to the apex of the heart by a wire. As the wire rotates, apical rotation (measured in degrees) can be calculated from the position of the deflected light beam. The timing of apical rotation was compared with simultaneous recordings of electrocardiogram, LV pressure, and LV diameter measurements. An initial clockwise rotation (untwist) of 4 +/- 2 degrees (SD) occurred during isovolumic contraction followed by counterclockwise rotation (twisting) through ejection, reaching maximum apical rotation of -15 degrees just before the end of systole. Rapid untwisting during isovolumic relaxation was shown with near-complete dissipation of twist by the first one-third of the diastolic filling period. Caval occlusion caused a downward and leftward shift of the pressure-apical rotation loops, and more twist/untwist was seen to occur during the respective isovolumic contraction and relaxation periods. We conclude that this device provides precise timing and definition of rapid changes during isovolumic contraction and relaxation, confirms results obtained by more laborious methods, and provides an easy method to measure the dynamics of apical rotation continuously during interventions such as load changes.
Effects of 2,3-butanedione monoxime on sarcoplasmic reticulum of saponin-treated rat cardiac muscle
Authors: Steele D. S. , Smith G. L.
Published: December 2017

We have studied the effects of 2,3-butanedione monoxime (BDM) on the sarcoplasmic reticulum (SR) of saponin-treated rat cardiac trabeculae. Rapid application of 20 mM caffeine released Ca2+ from the SR, which was detected using the fluorescent Ca2+ indicator indo 1. The amplitude of the caffeine-induced Ca2+ transient was used as an index of the Ca2+ content of the SR before, during, and after exposure to various concentrations of BDM. BDM (1-5 mM) had little effect on caffeine-induced Ca2+ release. At these levels of BDM, force was inhibited predominantly by a direct action of BDM on the myofilaments. However, with higher concentrations (5-30 mM), BDM caused a concentration-dependent decrease in the amount of Ca2+ released from the SR in response to caffeine. This action of BDM may contribute to the negative inotropic effect of the drug in intact cardiac preparations by reducing the amount of Ca2+ available for release during systole. Rapid application of BDM induced a net release of Ca2+ from the SR. Both BDM and caffeine-induced Ca2+ releases were abolished following treatment of the muscle with 10 microM ryanodine. BDM failed to release Ca2+ in the absence of ATP or after substitution of ATP with nonhydrolyzable adenine nucleotides. In contrast, caffeine released Ca2+ in the absence of ATP. The possible involvement of the Ca(2+)-uptake pump in the action of BDM on the SR is discussed.
Adenosine and cerebrovascular hyperemia during insulin-induced hypoglycemia in newborn piglet
Authors: Ruth V. J. , Park T. S. , Gonzales E. R. , Gidday J. M.
Published: December 2017

The present study tested the hypothesis that adenosine is involved in mediating the hyperemic response of the newborn brain to hypoglycemia. By use of the cranial window and microdialysis-H2 clearance methodologies, changes in the diameter of pial arterioles (25-50 microns), extracellular adenosine concentrations ([ADO]), and local cerebral blood flow (CBF) were examined in isoflurane-anesthetized piglets subjected to insulin-induced hypoglycemia. Blood glucose concentrations ranged from 10 to 18 mg/dl after insulin administration (25 IU/kg iv). Local CBF in the frontal cortex increased 36 +/- 12% (P = 0.014) at 30 min of hypoglycemia (group 1, n = 12; control = 43 +/- 3 ml.min-1.100 g-1). The mean increase in dialysate [ADO] sampled concurrently from the same cortical area was 59 +/- 29% (P = 0.011; control = 0.11 +/- 0.02 microM). At 30 min of hypoglycemia, pial diameters increased 55 +/- 10% (P = 0.001; group 2, n = 9). The [ADO] in cranial window cerebrospinal fluid (CSF) increased 217 +/- 71% (P = 0.04) in response to hypoglycemia (group 3, n = 8; control = 0.016 +/- 0.006 microM). Local administration of an adenosine antagonist, 10 microM 8-sulfophenyltheophylline, to the cerebral cortex before hypoglycemia caused a 38% reduction (P = 0.011) in the pial arteriolar response at 30 min of hypoglycemia (group 4, n = 9). Similarly, local superfusion of CSF with 3.7 mM glucose attenuated the hypoglycemia-induced pial dilation 33% (P = 0.039; group 5, n = 9). Perfusion of microdialysis probes with 3.7 mM glucose in the CSF abolished the hypoglycemia-induced increase in dialysate [ADO] (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis
Authors: Strony J. , Beaudoin A. , Brands D. , Adelman B.
Published: December 2017

Shear stress and alterations in blood flow within a stenosed artery promote platelet-dependent thrombosis. Using the Folts model of coronary thrombosis, we evaluated morphology, histology, and the hemodynamic properties of the stenosed vessel in 18 animals. The average stenosis created was 58 +/- 8%, with stenosed vessel diameters ranging from 0.084 to 0.159 cm. Histological examination of the stenosed vessel demonstrated that thrombi were composed primarily of platelets and formation occurred 1.0 mm downstream from the apex of the constriction, propagating distally. Peak shear stress occurred just upstream from the apex of the stenosis and varied from 520 to 3,349 dyn/cm2. Only small differences in shear forces were noted when blood viscosity was calculated using Newtonian and non-Newtonian properties. In contrast, shear stress computed for Poiseuille flow with use of the stenosis diameter underestimated the apical shear stress. Blood flow remained laminar within the stenosis with a Reynolds number range of 292-534. Our data indicate that the geometry of the stenosis inflow region must be considered in the evaluation of platelet activation and thrombus formation within a stenosed artery.
Diffusion permeability of the immature placenta of the rabbit embryo to inert hydrophilic molecules
Authors: Faber J. J.
Published: December 2017

The clearances of a series of hydrophilic probes (radii of 2-10 A) were determined in rabbit placentas of 13-15 days of gestation (term, 31 days). Maternal placental blood flows were measured by means of radiolabeled microspheres. None of the transfers of the tracers were limited by maternal or embryonic arteriovenous differences in the placenta, and the clearances decreased with increasing molecular radius. The transplacental water filtration rate calculated from conceptual growth was comparable in magnitude to the clearances of the largest tracers. Application of Patlak's modification of the Hertzian equation and pore theory suggested an equivalent pore radius of 17 A. Placental permeability surface area products computed from this value decreased much more steeply with increasing molecular dimension than the measured clearances, suggesting a highly significant contribution by filtration despite the very large diffusional gradients that existed under the experimental conditions. The results indicate that the size selectivity of the hemochorial embryo placenta in vivo is not very significant, and that under normal conditions filtrate of maternal plasma constitutes a major contributor to embryonic supply.
Enhanced myogenic activation in skeletal muscle arterioles from spontaneously hypertensive rats
Authors: Falcone J. C. , Granger H. J. , Meininger G. A.
Published: December 2017

The purpose of this study was to determine whether the vascular myogenic response is enhanced in hypertension. Experiments were conducted in the intact cremaster muscle microcirculation as well as in isolated arterioles of hypertensive (SHR) and normotensive (WKY) rats. Increasing venous pressure in vivo by approximately 5 mmHg had no effect on normotensive first- (1A) or third-order arteriolar (3A) diameters; in contrast, hypertensive 1A diameter decreased 4% (89 +/- 2 to 85 +/- 3 microns) with an 8% decrease in 3A (24 +/- 2 to 22 +/- 2 microns). To further examine this enhanced constriction to elevated intravascular pressure in SHR, diameter was monitored in isolated 1A during step increases and decreases in intraluminal pressure. Normotensive arterioles displayed myogenic responses between pressures of 50 and 170 cmH2O; in contrast, hypertensive arterioles demonstrated myogenic responses over an extended pressure range (50–210 cmH2O). In addition, the change in diameter for each step change in pressure was greater in the arterioles from SHR, indicating an increased myogenic responsiveness. The myogenic reactions were unaffected by alpha-receptor blockade with phentolamine (10(-6) M), indicating that adrenergic hypersensitivity was not involved in the enhanced response to stretch. Morphometric analysis of the vascular wall revealed no differences in wall thickness, cross-sectional wall area, or wall-to-lumen ratio between normotensive and hypertensive rats. The length-tension relationships for normotensive and hypertensive rats demonstrated that peak active tension occurred at nearly the same vascular smooth muscle length. In addition, SHR arterioles were capable of maintaining higher levels of active tension that WKY arterioles, indicating an altered length-tension curve in chronic arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Sieving of electrolytes at capillary wall of cat skeletal muscle by osmotic water flow
Authors: Watson P. D.
Published: December 2017

To test the hypothesis that a significant proportion of transcapillary water flow occurs through solute-restricting channels, we investigated the effects of transcapillary water movement on plasma electrolytes in isolated perfused cat skeletal muscle. The lower hindlimbs of anesthetized cats were perfused with a plasma-albumin solution and were weighed to determine transcapillary water movement. Osmolality was increased 60–70 mosmol/kgH2O with sucrose, creating water fluxes of 8–10 ml.min-1.100 g-1, and the changes in the venous concentrations of sodium, potassium, and chloride were determined. The ion concentrations were all reduced by 6–7% with no significant difference between them. The amount of reduction was quantitatively explained by the flow of ion-free water from the interstitial space into plasma and the diffusion of electrolyte in the same direction. These findings support the hypothesis that important water-only transcapillary channels exist in mammalian skeletal muscle. The observations may also explain some of the electrolyte changes seen in intense exercise.
Thyroxine effects on temperature dependence of ionic currents in single rabbit cardiac myocytes
Authors: Shimoni Y. , Banno H.
Published: December 2017

Macroscopic whole cell currents were measured from single rabbit cardiac myocytes, using the suction electrode voltage-clamp technique, under euthyroid, hyperthyroid, and hypothyroid conditions. In ventricular myocytes, the temperature dependence of the transient outward current (I(t)) was greatly reduced in hyperthyroid conditions, with Q10 values (between 22 and 32 degrees C) reduced from normal values of 6.14 +/- 0.93 (SE, n = 8) to 2.14 +/- 0.14 (n = 6). In contrast, two of the other major currents in these cells were relatively unaffected. Under hyperthyroid conditions, there was very little change in the amplitudes or temperature dependence of L-type calcium currents and of steady-state currents, which reflect mainly the inwardly rectifying potassium current. In atrial cells no changes in the temperature dependence of I(t) were observed, with virtually identical Q10 values (close to 4) in eu- and hyperthyroid conditions. Under hypothyroid conditions, there was no change in the temperature dependence of I(t) in either ventricular or atrial cells. We conclude that the regulation of I(t) in ventricular cells is unique, rendering it extremely sensitive to temperature changes and to elevations in thyroxine levels. These results are discussed in the context of long-term regulation of ionic channels.
Ventricular interaction is described by three coupling coefficients
Authors: Taher M. F. , Santamore W. P. , Bogen D. K.
Published: December 2017

Previous studies of ventricular interaction have quantified interaction by making small pressure or volume changes in one ventricle and measuring the resulting pressure or volume changes in the opposite ventricle. The ratios between the pressure and volume changes in opposite ventricles have been used as coupling coefficients or measures of ventricular interaction. This method of calculating coupling coefficients implicitly uses mathematical relationships that have useful features not generally appreciated. Starting from the definition of coupling coefficients we show that, without making any assumptions about ventricular interaction, all 24 possible coupling coefficients can be derived from a smaller set of four coupling coefficients. Furthermore, by making the single assumption that the ventricles behave elastically, we show that the set of four coefficients can be reduced to a set of three. Thus only three indexes are required to describe interaction, but these may vary with changes in ventricular volumes and pressures around which the indexes are measured. Furthermore, when comparisons between experimental studies are made, it is necessary to normalize the indexes with respect to ventricular volume.
Transfer function analysis from arterial baroreceptor afferent activity to renal nerve activity in rabbits
Authors: Imaizumi T. , Harasawa Y. , Ando S. , Sugimachi M. , Takeshita A.
Published: December 2017

In vagotomized and anesthetized rabbits, aortic pressure (AP), aortic depressor nerve activity (ANA), and renal sympathetic nerve activity (RNA) were simultaneously measured while perturbing AP randomly. To quantitatively characterize the role of the arterial baroreflex system in generating RNA, we determined the transfer function (TF) of the central baroreflex arc from ANA to RNA in the frequency domain (0.02–5 Hz). The magnitude of squared coherence was > 0.5, the phase was close to -180 degrees, and the gain of TF was flat over 0.02–0.3 Hz, indicating that changes in RNA were linearly and instantaneously but inversely related to changes in ANA over this frequency range. Above 0.3 Hz, the coherence was low, suggesting that RNA unrelated to ANA existed in the frequency range. In animals without AP perturbations, power spectrum of RNA resided over 0.2–5 Hz with a broad peak at 1 Hz, which may represent central activity. Our results suggest that over 0.02–0.3 Hz the relationship between arterial baroreceptor afferent nerve activity and RNA is linear and instantaneous but above 0.3 Hz it is not linear possibly due to an interaction between central activity and arterial baroreflex.
Modulation of sympathetic nerve activity during posthandgrip muscle ischemia in humans
Authors: Ray C. A. , Secher N. H. , Mark A. L.
Published: December 2017

To evaluate modulation of muscle sympathetic nerve activity (MSNA) during posthandgrip muscle ischemia (PHGMI), subjects performed 2 min of isometric handgrip at 33% of maximal voluntary contraction (MVC) followed by 2 min of PHGMI produced by forearm vascular occlusion. The response to PHGMI was studied in the absence and again during the addition of contralateral rhythmic handgrip (RHG; 40 times/min) at 15% (n = 6) and 30% (n = 10) MVC during the second minute of the PHGMI. Additionally, to isolate the effect of central command, response to PHGMI was studied during attempted RHG after sensory nerve blockade (n = 5). RHG for 2 min at 15 and 30% MVC and attempted RHG for 2 min did not increase MSNA. Isometric handgrip elicited an 130 +/- 48% increase in MSNA (P < 0.05), which was maintained during PHGMI. RHG at 15 and 30% MVC elicited an attenuation of MSNA (-10 +/- 7% and -14 +/- 6%, respectively) when performed during the second minute of PHGMI (P < 0.05). In contrast, attempted RHG did not significantly affect MSNA during PHGMI. The findings demonstrate modulation of MSNA during activation of the muscle metaboreflex. The attenuation of metaboreceptor-mediated increases in MSNA appear to be the result of mechanosensitive muscle afferents and not central command.
Dietary Na and baroreflex modulation of blood pressure and RSNA in normotensive vs. spontaneously hypertensive rats
Authors: Huang B. S. , Leenen F. H.
Published: December 2017

Different changes in baroreflex control of the circulation have been postulated to play a role in the different blood pressure (BP) effects of dietary sodium in normotensive vs. genetically hypertensive rats. We therefore evaluated in young Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), with or without chronic sinoaortic denervation (SAD), the effects of low, regular, and high dietary sodium intake from 4 to 8 wk of age on BP and baroreflex function. The latter was assessed by changes in renal sympathetic nerve activity (RSNA) and heart rate in response to (de)pressor agents. In SHR, the above range of sodium caused a marked change in resting BP, somewhat more in intact (48 mmHg) vs. SAD (36 mmHg) rats. In contrast, in WKY this range of sodium intake caused only a minor (7 mmHg) change in resting BP of intact WKY but a significant (16 mmHg) change in WKY with SAD, mainly due to an increase in BP on high sodium. In intact WKY increasing dietary sodium from low to regular to high caused stepwise increases in the gain of the RSNA-BP reflex, whereas in intact SHR only an increase from low to regular sodium intake increased the gain. After SAD, the gain of the RSNA-BP reflex was very low, and no longer affected by dietary sodium in either strain. These data suggest that in WKY a sensitization in arterial baroreflex control of RSNA prevents a sodium-induced increase in BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial work load is a major determinant of norepinephrine-induced left ventricular dysfunction
Authors: Bosso F. J. , Allman F. D. , Pilati C. F.
Published: December 2017

This study was conducted to determine whether increased myocardial energy demand plays a role in norepinephrine (NE)-induced left ventricular (LV) dysfunction. A range of arterial pressure-heart rate (P-R) products (myocardial energy demand) was produced in both conscious and pentobarbital sodium-anesthetized rabbits with the same dose of NE (10 micrograms priming bolus plus 2.5 micrograms.kg-1 x min-1 for 2.5 h). After NE treatment, LV function was evaluated in vitro and found to be markedly diminished in the rabbits that had an elevated P-R product. In contrast, LV function was not significantly affected when the P-R product was maintained near control levels during NE treatment. In separate experiments, rabbit hearts were isolated and exposed to NE (10,000 or 50,000 pg/ml) for 2.5 h under low P-R product conditions. These hearts exhibited a dose-dependent decrease in LV function that was modest compared with that observed in rabbits that had elevated P-R products during in vivo NE treatment. Our results suggest that high concentrations of NE may cause modest degrees of LV dysfunction independently of increases in myocardial energy demand, but the LV dysfunction is exacerbated when myocardial energy demand is elevated.
Inhibitory effects of cocaine on Ca2+ transients and contraction in single cardiomyocytes
Authors: Renard D. C. , Delaville F. J. , Thomas A. P.
Published: December 2017

The effects of cocaine on the Ca2+ transient responsible for excitation-contraction coupling were studied in single rat heart cells loaded with the fluorescent Ca2+ indicator fura 2. A high-speed imaging technique using a charge-coupled device as detector and transient image store [O'Rourke et al., Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H230-H242, 1990] was used to measure cytosolic free Ca2+ concentration ([Ca2+]i) and contraction simultaneously from the images of fluorescence. Cardiomyocytes maintained a basal [Ca2+]i of approximately 140 nM in presence or absence of cocaine. After electrical field stimulation, [Ca2+]i increased to a peak of 498 +/- 25 nM under control conditions. This was reduced to a peak [Ca2+]i of 389 +/- 25 nM after treatment with 50 microM cocaine. Cocaine also reduced the rate of rise of [Ca2+]i but did not affect the time to peak or the half time for resequestration of the released Ca2+. The rate and extent of cell shortening was reduced by cocaine in parallel with the inhibition of the [Ca2+]i transient. Cocaine had no effect on the half time for relaxation. Cocaine did not modify the relationship between contraction and the elevation of [Ca2+]i over a range of extracellular Ca2+ concentrations. The intracellular pool of Ca2+ releasable by caffeine was also unaffected by cocaine. In the presence of the beta-adrenergic agonist isoproterenol, which caused a large enhancement of peak [Ca2+]i and contraction, cocaine still inhibited both parameters. However, cocaine did not reverse the ability of isoproterenol to enhance the rate of Ca2+ reuptake and cell relaxation. Whole cell voltage-clamp studies showed that 50 microM cocaine reduced both the Na+ current (50%) and the Ca2+ current (30%). These data suggest that sarcolemmal ion channels are the primary site that, in cardiac muscle, mediate the negative inotropic effects and the suppression of [Ca2+]i transients by cocaine.
Role of endothelium-derived nitric oxide in stimulation of Na(+)-K(+)-ATPase activity by endothelin in rabbit aorta
Authors: Gupta S. , McArthur C. , Grady C. , Ruderman N. B.
Published: December 2017

An endothelium-derived factor with the properties of nitric oxide (NO) has recently been implicated in the regulation of basal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To determine whether this factor also plays a role in the stimulation of ouabain-sensitive (OS) 86Rb uptake by specific agonists, studies were carried out using rabbit aortic rings. In endothelium-intact rings incubated for 3 h with Krebs-Henseleit solution containing 5.5 mM glucose, endothelin (ET) caused a concentration-dependent increase in OS 86Rb uptake (maximal increase = 205%, with 100 nM ET). Incubation with phenylephrine (Phe; 0.1 and 1 microM) or phorbol 12,13-dibutyrate (PDBu; 0.1 microM), under the same conditions, increased OS 86Rb uptake by 128, 144, and 140%, respectively. Removal of endothelium before incubation decreased the ability of ET to stimulate OS 86Rb uptake by 38–45%, but it did not diminish the stimulation of OS 86Rb uptake by Phe or PDBu. An increase in the concentration of glucose from 5.5 to 44 mM diminished ET-stimulated OS 86Rb uptake by 50% in endothelium-intact rings but had no effect on Phe- or PDBu-induced increases in OS 86Rb uptake. Addition of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 0.3 mM) to the medium decreased ET-stimulated OS 86Rb uptake by 40%. Guanosine 3',5'-cyclic monophophate (cGMP) formation in endothelium-intact rings was also increased (65%) by ET but not by Phe or PDBu. The increase in cGMP by ET was totally inhibited by L-NMMA or endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)
[Ca2+]i and protein kinase C in vasopressin-induced prostacyclin and ANP release in rat cardiomyocytes
Authors: Van der Bent V. , Church D. J. , Vallotton M. B. , Meda P. , Kem D. C. , Capponi A. M. , Lang U.
Published: December 2017

Exposure of cultured, spontaneously beating rat cardiomyocytes to arginine vasopressin (AVP) led to marked increases in the release of prostacyclin (PGI2) and atrial natriuretic peptide (ANP). These responses were accompanied by a rapid, transient rise of cytosolic free Ca2+ concentration ([Ca2+]i) and of membranous protein kinase C (PKC) activity. Ca2+ influx and PKC activity appeared to play important but distinct roles in AVP-induced cellular responses, insofar as only AVP-induced ANP secretion was abolished by the Ca2+ channel antagonist nifedipine, whereas both AVP-induced PGI2 production and ANP release were abolished by the PKC inhibitors staurosporine and CGP-41251. The AVP-induced increase in [Ca2+]i could also be mimicked with the vasopressin (V1-subtype) agonist Octapressin, but not with the V2-agonist 1-desamino-8-D-arginine vasopressin, and was fully abolished by the V1-antagonist [d(CH2)5Tyr(Me)]AVP, but not by d(CH2)5-D-Leu-VAVP (V1-/V2-antagonist). These results indicate that V1-vasopressinergic receptors mediate AVP-induced PGI2 production and ANP secretion in rat cardiomyocytes and that, whereas both Ca2+ influx and PKC activation are required for AVP-induced ANP secretion, AVP-induced PGI2 formation is mainly regulated by PKC.
Light/dye microvascular injury selectively eliminates hypercapnia-induced pial arteriolar dilation in newborn pigs
Authors: Leffler C. W. , Mirro R. , Shanklin D. R. , Armstead W. M. , Shibata M.
Published: December 2017

Cerebral vasodilation in response to hypercapnia involves prostanoids in newborn pigs. This study examines the hypothesis that endothelial injury in vivo inhibits cerebral vasodilation and prostacyclin synthesis in response to hypercapnia, thus suggesting prostacyclin is a primary endothelium-derived vasodilating factor in newborn pig cerebral circulation. Anesthetized piglets with closed cranial windows were studied before and after injury caused by light/dye or before and after dye-only sham control. Light/dye injury was produced by injecting sodium fluorescein intravenously and passing filtered light from a mercury arc lamp through the cranial window. Ultrastructural changes to endothelium of pial vessels were produced that were characterized by surface pits, vacuolar cytoplasmic inclusions, and mitochondrial injury. After the light/dye injury, dilation to hypercapnia was absent while dilations to iloprost, isoproterenol, and sodium nitroprusside and constrictions to norepinephrine and acetylcholine were retained. Before light/dye treatment, hypercapnia increased cortical periarachnoid 6-keto prostaglandin F1 alpha concentration approximately threefold. However, after treatment, 6-keto-prostaglandin F1 alpha was not increased significantly in response to hypercapnia. These findings are consistent with the hypothesis that endothelial prostacyclin synthesis induced by hypercapnia participates in dilation of adjacent smooth muscle.
ANG II receptor expression and function during phenotypic modulation of rat aortic smooth muscle cells
Authors: Corriu C. , Andre P. , Schott C. , Michel M. , Stoclet J. C.
Published: December 2017

Angiotensin II (ANG II) receptors were investigated in primary cultured rat aortic smooth muscle cells (SMC) that expressed either a proliferative phenotype (during the growth phase) or a contractile phenotype (at postconfluence). For each phenotype, alpha-smooth muscle actin expression, 125I-labeled ANG II specific binding, D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] production, and ANG II-mediated increases in intracellular calcium (Cai2+) were studied. In both phenotypes, 1) ANG II-specific high-affinity binding (KD 0.5 +/- 0.1 nM and Bmax 196 +/- 106 pmol/mg protein in proliferative state, KD 1.5 +/- 0.3 nM and Bmax 560 +/- 299 pmol/mg protein in postconfluent state) was entirely inhibited by the selective AT1-antagonist losartan as well as by [Sar1,Ala8]ANG II and ANG III; 2) the AT2-antagonist CGP 42112A was ineffective, except at very high concentrations (> or = 10 microM); 3) the specific binding of ANG II was inhibited by guanosine 5'-[gamma-thio]triphosphate; and 4) ANG II induced a losartan-sensitive increase in Ins(1,4,5)P3. In postconfluent cultures, ANG II elicited a rapid biphasic elevation in Cai2+, which was abolished by losartan, whereas in growing cultures, this response was either absent or greatly attenuated. It is concluded that AT1-receptors coupled to phospholipase C via a G protein are expressed in the proliferative as well as in the contractile SMC phenotype and that their coupling to Cai2+ release is impaired in the proliferative phenotype. No evidence for AT2-receptor expression during phenotypic modulation of SMC was found.
Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo
Authors: Gaboury J. P. , Anderson D. C. , Kubes P.
Published: December 2017

Intravital microscopy was used to monitor leukocyte adherence, flux, rolling velocity, and number of rolling leukocytes (flux/velocity) in venules 25–40 microns in diameter. The superoxide-generating system, hypoxanthine and xanthine oxidase (HX/XO), was infused into the mesenteric circulation in untreated animals or in animals pretreated with either catalase (a hydrogen peroxide scavenger), WEB-2086 [a platelet-activating factor (PAF) receptor antagonist], or monoclonal antibodies directed against adhesion molecules CD18 (CL26) or P-selectin (PB1.3). HX/XO infusion caused a decrease in leukocyte rolling velocity and an increase in the number of rolling and adherent leukocytes. WEB-2086 prevented the increase in leukocyte adhesion and markedly increased leukocyte rolling velocity. PB1.3 abolished the HX/XO-associated rise in the flux of rolling leukocytes and proportionally decreased the number of adherent leukocytes. CL26 abolished HX/XO-induced leukocyte adhesion and also reduced the number of rolling leukocytes. In conclusion, P-selectin mediates the increased leukocyte flux induced by superoxide, whereas PAF and CD18 modulate leukocyte adhesion. PAF also reduces leukocyte rolling velocity, possibly as a result of CD18, but not P-selectin.
Mechanics of large and small cerebral arteries in chronic hypertension
Authors: Hajdu M. A. , Baumbach G. L.
Published: December 2017

The goal of this study was to investigate factors that contribute to reductions in internal diameter of large and small cerebral arteries during chronic hypertension. We measured diameter of second- and third-order branches of the posterior cerebral artery in vitro during maximal dilation with EDTA in 6-mo-old stroke-prone spontaneously hypertensive rats (SHRSP, n = 7) and Wistar-Kyoto rats (WKY, n = 7). Cross-sectional area of the vessel wall, measured histologically, was not significantly different at 70 mmHg in SHRSP and WKY in large or small branches of posterior cerebral artery. In large branches of posterior cerebral artery, external and internal diameters were significantly less at 70 mmHg in SHRSP than in WKY, whereas external and internal diameters converged at 0 mmHg in the two groups of rats. In small branches, on the other hand, external and internal diameters were significantly less at all levels of intravascular pressure in SHRSP than in WKY. The stress-strain relation in posterior cerebral artery of SHRSP was shifted to the left in large branches and to the right in small branches, which indicates that distensibility was reduced in large cerebral arteries of SHRSP and increased in small cerebral arteries. These findings suggest that different mechanisms are responsible for impairment of maximal dilator capacity in large and small cerebral arteries of SHRSP: reduced distensibility in large arteries and remodeling with reduced external diameter in small arteries. Furthermore the findings provide additional support for the concept that hypertrophy may not be a primary factor in impaired maximal dilation.
Arteriolar network response to pressure reduction during sympathetic nerve stimulation in cat skeletal muscle
Authors: Ping P. , Johnson P. C.
Published: December 2017

Previous studies in this laboratory have shown that autoregulation of blood flow and dilation of midsized (second-order) arterioles were significantly enhanced during sympathetic nerve stimulation of cat sartorius muscle apparently because of a greater myogenic response of the arterioles. Quite typically, blood flow increased with arterial pressure reduction to 80, 60, and 40 mmHg (superregulation) during sympathetic nerve stimulation. To determine the contribution of the various orders of arterioles to the enhanced autoregulation, we measured diameters in all orders of arterioles and measured red cell velocity in first-, second-, and third-order arterioles. Without sympathetic nerve stimulation, all orders of arterioles except the first order dilated to pressure reduction, but flow autoregulation was weak. With sympathetic nerve stimulation, arteriolar dilation to pressure reduction was significantly enhanced in all six orders of arterioles, and flow rose significantly. The resistance change in the arteriolar network during pressure reduction as calculated from diameter changes was greatest in third- and fourth-order arterioles. Experimentally determined flow changes to pressure reduction and to sympathetic nerve stimulation were quantitatively similar to those predicted from diameter changes in a model of the arteriolar network. Calculated wall shear stress (from viscosity and shear rate) for first-, second-, and third-order arterioles decreased during pressure reduction with and without sympathetic nerve stimulation. We concluded that endothelium-mediated dilation due to shear stress would tend to oppose autoregulation of blood flow to a similar degree under both circumstances.
Noninvasive measurement of left ventricular myocardial elasticity
Authors: Honda H. , Koiwa Y. , Takagi K. , Kikuchi J. , Hoshi N. , Takishima T. , Butler J. P.
Published: December 2017

We examined Advani and Lee's equation (ALeq) and a dimension analysis-derived equation (DAeq), both of which treat vibration of the elastic spherical shell and are able to estimate elasticity of the shell noninvasively when the sizes and eigen-frequency are provided. We confirmed that ALeq was numerically identical to DAeq and that both equations gave the precise elasticity of the silicone shell. Then we estimated left ventricular (LV) myocardial elasticity noninvasively at the moment of the first heart sound emission (1HS) in 25 healthy subjects and 14 hypertrophic cardiomyopathy (HCM) patients, based on the LV eigen-frequency detected by an intraesophageal miniature vibration sensor. HCM patients had a higher mean value of LV myocardial elasticity at 1HS than healthy subjects [102.3 +/- 33.4 vs. 70.7 +/- 24.4 kPa, P < 0.01 (Pa = N/m2 = 10 dyn/cm2)]. We thereby demonstrated the possibility of a noninvasive estimate of myocardial elasticity.
Vasodilation by shear-induced platelet aggregation in extracorporeal circuits
Authors: Borgdorff P. , Kok W. E. , Vis M. A. , van den Bos G. C.
Published: December 2017

Extracorporeal circulation may have adverse effects on vascular reactivity. To reduce such effects, we recently coated a tube connecting the carotid and the distal femoral artery of rats with albumin. When we partially occluded this perfusion line, the reduction of flow was followed by a marked increase, which seemed not to be caused by autoregulation but by release of a vasodilator at the site of occlusion. In the present study, we investigated whether this vasodilator could originate from platelets aggregating under the influence of increased shear stress at the site of occlusion. Blood distal to the site of occlusion indeed contained numerous platelet aggregates that were not present before occlusion. Continuous recording with a photometric device showed that aggregation in the tube started before flow increased and ended before flow decreased again. Blockade of serotonin S1- and S2-receptors with methiothepin prevented the flow response. Estimated shear stress (231 +/- 17 dyn/cm2) and shear rate (6,370 +/- 478 s-1) at the site of occlusion were of the magnitude known to elicit platelet aggregation. Others have recently demonstrated that shear-induced platelet aggregation is mediated by binding of von Willebrand factor to platelet glycoprotein Ib, which is inhibited by aurintricarboxylic acid. This drug (35 mg/kg iv) completely abolished both platelet aggregation and flow increase in our experiments. These results suggest that the vasodilation during partial tube occlusion is mediated by serotonin released from platelets that aggregate as a result of high shear stress.
EDRF in pulmonary resistance vessels from fetal lamb: stimulation by oxygen and bradykinin
Authors: Wang Y. , Coceani F.
Published: December 2017

Endothelium-derived relaxing factor-nitric oxide (EDRF-NO) has been studied in isolated, pulmonary resistance vessels from term fetal lambs at a fetal (21 +/- 0.2 mmHg) and neonatal (69 +/- 0.4 mmHg) PO2. Bradykinin dose dependently (0.1-100 nM) relaxed arteries and veins that had been precontracted with a thromboxane A2 analogue. Their response did not differ at low PO2, whereas the response of the arteries was greater at high PO2. Sodium nitroprusside was almost as potent as bradykinin on the arteries, but its action did not vary with PO2. Acetylcholine also relaxed the arteries at higher concentrations (0.1-100 microM). N omega-mono-methyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) (both at 100 microM) weakly contracted arteries at low PO2. The contraction to L-NAME, but not L-NMMA, increased with the PO2. In the arteries, L-NAME had no effect on bradykinin relaxation at low PO2, whereas it was an inhibitor at high PO2. Conversely, L-NMMA slightly inhibited bradykinin relaxation regardless of PO2. In the veins, L-NAME transiently increased basal tone and inhibited bradykinin relaxation at either PO2. Indomethacin (2.8 microM) had no effect on arteries at low PO2, whereas it was a constrictor at high PO2. No indomethacin constriction occurred in the veins. We conclude that fetal pulmonary resistance vessels possess an EDRF-NO relaxing mechanism that is stimulated by bradykinin. In the arteries, this mechanism is more effective at high PO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Human uterine arterial relaxation induced by nitroxidergic nerve stimulation
Authors: Toda N. , Kimura T. , Yoshida K. , Bredt D. S. , Snyder S. H. , Yoshida Y. , Okamura T.
Published: December 2017

Uterine arterial strips obtained from humans responded to nicotine with a contraction, which was abolished by prazosin. In the arteries treated with the alpha 1-receptor antagonist and partially contracted with serotonin, nicotine produced a relaxation that was not influenced by treatment with atropine or timolol and endothelium denudation but was abolished by hexamethonium, oxyhemoglobin, and NG-nitro-L-arginine (L-NNA). The inhibitory effect of L-NNA was reversed by L- but not D-arginine. Relaxations induced by nitroglycerin and nitric oxide (NO) were not affected by L-NNA but were abolished by oxyhemoglobin. Transmural electrical stimulation relaxed the arterial strips treated with prazosin; this response was abolished by L-NNA and restored by L-arginine. Histochemical study with NO synthase antiserum demonstrated the presence of immunoreactive nerve fibers in the adventitia. It may be concluded that human uterine arteries are innervated by vasodilator nerves that liberate NO as a neurotransmitter after chemical or electrical stimulation. Predominant vasoconstriction due to nerve stimulation appears to be associated with activation of alpha 1-adrenoceptors by neurogenic norepinephrine.