bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural properties of rat mesenteric small arteries after 4-wk exposure to elevated or reduced blood flow
Authors: Pourageaud Fabrice , De Mey Jo G. R.
Published: December 2017

We determined the structure of mesenteric small arteries after chronic elevation and chronic reduction of blood flow. In 6-wk-old rats, we ligated second-order side branches of every other first-order side branch of the superior mesenteric artery. This persistently reduced blood flow (−90%) in the vessels feeding into the ligated trees and elevated blood flow (+80%) in the nonligated mesenteric artery side branches. Four weeks after surgery, vessels that had been exposed to high blood flow (HF) or low blood flow (LF) and vessels from sham-operated rats (Sham) were isolated and mounted in a pressure myograph system. At an intraluminal pressure of 100 mmHg, the internal diameter at rest was larger in HF (533 ± 23 μm) and smaller in LF (262 ± 14 μm) than in Sham vessels (427 ± 15 μm). Also, wall and media cross-sectional areas were larger in HF and smaller in LF than in Sham vessels (media: 22 ± 1, 11 ± 2, and 16 ± 1 × 103μm2, respectively), but circumferential wall stress did not differ among groups. DNA content was significantly increased in HF vessels (+100%) and was not modified in LF vessels. Maximal vasoconstrictions elicited by high potassium or norepinephrine were slightly increased in HF vessels but were reduced by 50% in LF vessels. Thus chronic changes in blood flow give rise to structural changes that normalize circumferential wall stress. Elevated blood flow resulted in outward hypertrophic remodeling involving hyperplasia. Reduced blood flow resulted in inward hypotrophic remodeling accompanied by hyporeactivity of the arterial smooth muscle.
Sleep and circadian influences on cardiac autonomic nervous system activity
Authors: Burgess Helen J. , Trinder John , Kim Young , Luke David
Published: December 2017

To assess the separate contributions of the sleep and circadian systems to changes in cardiac autonomic nervous system (ANS) activity, 12 supine subjects participated in two 26-h constant routines, which were counterbalanced and separated by 1 wk. One routine did not permit sleep, whereas the second allowed the subjects to sleep during their normal sleep phase. Parasympathetic nervous system activity was assessed with respiratory sinus arrhythmia as measured from the spectral analysis of cardiac beat-to-beat intervals. Sympathetic nervous system activity was primarily assessed with the preejection period as estimated from impedance cardiography, although the 0.1-Hz peak from the spectral analysis of cardiac beat-to-beat intervals, the amplitude of the T wave in the electrocardiogram, and heart rate were also measured. Respiratory sinus arrhythymia showed a 24-h rhythm independent of sleep, whereas preejection period only showed a 24-h rhythm if sleep occurred. Thus the findings indicate that parasympathetic nervous system activity is mostly influenced by the circadian system, whereas sympathetic nervous system activity is mostly influenced by the sleep system.
Cardiovascular responses to dynamic exercise with acute anemia in humans
Authors: Koskolou Maria D. , Roach Robert C. , Calbet José A. L. , Rådegran Göran , Saltin Bengt
Published: December 2017

We hypothesized that reducing arterial O2 content ([Formula: see text]) by lowering the hemoglobin concentration ([Hb]) would result in a higher blood flow, as observed with a low [Formula: see text], and maintenance of O2 delivery. Seven young healthy men were studied twice, at rest and during two-legged submaximal and peak dynamic knee extensor exercise in a control condition (mean control [Hb] 144 g/l) and after 1–1.5 liters of whole blood had been withdrawn and replaced with albumin {mean drop in [Hb] 29 g/l (range 19–38 g/l); low [Hb]}. Limb blood flow (LBF) was higher ( P < 0.01) with low [Hb] during submaximal exercise (i.e., at 30 W, LBF was 2.5 ± 0.1 and 3.0 ± 0.1 l/min for control [Hb] and low [Hb], respectively; P < 0.01), resulting in a maintained O2 delivery and O2 uptake for a given workload. However, at peak exercise, LBF was unaltered (6.5 ± 0.4 and 6.6 ± 0.6 l/min for control [Hb] and low [Hb], respectively), which resulted in an 18% reduction in O2 delivery ( P < 0.01). This occurred despite peak cardiac output in neither condition reaching >75% of maximal cardiac output (∼26 l/min). It is concluded that a low CaO2 induces an elevation in submaximal muscle blood flow and that O2 delivery to contracting muscles is tightly regulated.
Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets
Authors: Chen Liying , Salafranca Mina N. , Mehta Jawahar L.
Published: December 2017

Activity of both nitric oxide (NO) synthase (NOS) and cyclooxygenase (COX) plays an important role in the regulation of platelet function. NO has been shown to directly activate COX. This study was designed to determine whether products of the COX pathway in turn regulate NOS activity. Human platelets were incubated with aspirin, indomethacin, the selective thromboxane A2synthase inhibitor U-63557A, or the prostaglandin H2-thromboxane A2-receptor blocker SQ-29548 for 1 h at 37°C. Multiple indexes of the activity of thel-arginine-NO pathway and changes in cytosolic Ca2+concentration ([Ca2+]i) were measured in platelets. Both aspirin and indomethacin decreased NOS activity, measured as the conversion ofl-arginine tol-citrulline and nitrite (+nitrate) formation, in platelets in a concentration-dependent fashion. Aspirin also decreased guanosine 3′,5′-cyclic monophosphate accumulation in platelets. The NOS inhibitory effects of these aspirin and indomethacin effects were reversed by coincubation with the thromboxane A2analog U-46619 or an excess of CaCl2. Incubation of COX inhibitors with platelets was associated with significant reductions in basal as well as thrombin-stimulated [Ca2+]i, and the reduction in [Ca2+]iwas reversed by U-46619. Incubation of platelets with U-63557A and SQ-29548 resulted in inhibitory effects on NOS activity qualitatively similar to those of COX inhibitors. The effects of COX inhibitors or U-63557A were not associated with a change in NOS protein expression in platelets. These data suggest that NOS activity in human platelets is inhibited by COX inhibitors, mediated, at least in part, via suppression of thromboxane A2and [Ca2+]imobilization in platelets.
Three-dimensional residual strain in midanterior canine left ventricle
Authors: Costa Kevin D. , May-Newman Karen , Farr Dyan , O’Dell Walter G. , McCulloch Andrew D. , Omens Jeffrey H.
Published: December 2017

All previous studies of residual strain in the ventricular wall have been based on one- or two-dimensional measurements. Transmural distributions of three-dimensional (3-D) residual strains were measured by biplane radiography of columns of lead beads implanted in the midanterior free wall of the canine left ventricle (LV). 3-D bead coordinates were reconstructed with the isolated arrested LV in the zero-pressure state and again after local residual stress had been relieved by excising a transmural block of tissue. Nonhomogeneous 3-D residual strains were computed by finite element analysis. Mean ± SD ( n = 8) circumferential residual strain indicated that the intact unloaded myocardium was prestretched at the epicardium (0.07 ± 0.06) and compressed in the subendocardium (−0.04 ± 0.05). Small but significant longitudinal shortening and torsional shear residual strains were also measured. Residual fiber strain was tensile at the epicardium (0.05 ± 0.06) and compressive in the subendocardium (−0.01 ± 0.04), with residual extension and shortening, respectively, along structural axes parallel and perpendicular to the laminar myocardial sheets. Relatively small residual shear strains with respect to the myofiber sheets suggest that prestretching in the plane of the myocardial laminae may be a primary mechanism of residual stress in the LV.
Cerebral circulatory responses of near-term ovine fetuses during sustained fetal placental embolization
Authors: Gagnon Robert , Lamb Tasha , Richardson Bryan
Published: December 2017

To test the hypothesis that, in response to an increase in placental vascular resistance and progressive fetal asphyxia, the changes in external carotid blood flow waveforms are directly related to changes in external carotid vascular resistance, we embolized the fetal side of the placenta in pregnant sheep and measured cerebral and external carotid artery circulatory changes in relation to changes in external carotid artery flow waveforms. Chronically catheterized fetal sheep at 0.85 of gestation were embolized ( n = 11) in the descending aorta for 6 h, until fetal arterial pH fell to ∼6.90. Fetuses became rapidly hypoxemic ( P < 0.0001) and developed a mixed respiratory and metabolic acidosis ( P< 0.0001 for [Formula: see text], pH, and base excess). There was a transient 40% increase in external carotid blood flow at pH ∼7.25 and a parallel 32% increase in fetal arterial blood pressure (both P < 0.01), whereas the external vascular resistance remained unaltered. Cerebral blood flow increased by 130% ( P < 0.0001), and cerebral vascular resistance decreased by 125% ( P < 0.0001) throughout the study. The external carotid resistance index (RI) decreased by 32% ( P < 0.0001) at the time external carotid vascular resistance remained unchanged. This fall in external carotid RI was due almost entirely to a 110% increase in external carotid fundamental impedance ( P < 0.001). We conclude that the poor relationship between the changes in external carotid vascular resistance and RI indicated that other hemodynamic factors such as vascular impedance to pulsatile flow must be measured for correct interpretation of changes in flow waveform shape under hypoxic conditions. In addition, changes in external carotid blood flow were not proportional to changes in cerebral blood flow in this model.
Spectral characteristics of ventricular response to atrial fibrillation
Authors: Hayano Junichiro , Yamasaki Fumiyasu , Sakata Seiichiro , Okada Akiyoshi , Mukai Seiji , Fujinami Takao
Published: December 2017

To investigate the spectral characteristics of the fluctuation in ventricular response during atrial fibrillation (AF), R-R interval time series obtained from ambulatory electrocardiograms were analyzed in 45 patients with chronic AF and in 30 age-matched healthy subjects with normal sinus rhythm (SR). Although the 24-h R-R interval spectrum during SR showed a 1/ f noise-like downsloping linear pattern when plotted as log power against log frequency, the spectrum during AF showed an angular shape with a breakpoint at a frequency of 0.005 ± 0.002 Hz, by which the spectrum was separated into long-term and short-term components with different spectral characteristics. The short-term component showed a white noise-like flat spectrum with a spectral exponent (absolute value of the regression slope) of 0.05 ± 0.08 and an intercept at 10−2 Hz of 4.9 ± 0.3 log(ms2/Hz). The long-term component had a 1/ f noise-like spectrum with a spectral exponent of 1.26 ± 0.40 and an intercept at 10−4 Hz of 7.0 ± 0.3 log(ms2/Hz), which did not differ significantly from those for the spectrum during SR in the same frequency range [spectral exponent, 1.36 ± 0.06; intercept at 10−4 Hz, 7.1 ± 0.3 log(ms2/Hz)]. The R-R intervals during AF may be a sequence of uncorrelated values over the short term (within several minutes). Over the longer term, however, the R-R interval fluctuation shows the long-range negative correlation suggestive of underlying regulatory processes, and spectral characteristics indistinguishable from those for SR suggest that the long-term fluctuations during AF and SR may originate from similar dynamics of the cardiovascular regulatory systems.
Variability of R-R, P wave-to-R wave, and R wave-to-T wave intervals
Authors: Forester J. , Bo H. , Sleigh J. W. , Henderson J. D.
Published: December 2017

We analyzed the effect of changing posture from supine to standing on the variability of R-R, P-R, and R-T intervals in 10 healthy volunteers using power spectral analysis. An electrocardiogram and respiratory trace were recorded before and after posture change. Variability in the P-R and R-T intervals was much less than in the R-R interval and demonstrated a lower low-frequency (LF)-to-high-frequency (HF) ratio. Changing from a supine to a standing position showed no change in indexes of vagal influence on the P-R and R-T variability, in contrast to the well-documented decrease in the indexes of vagal influence on the R-R variability (HF power decreased from 2.33 to 0.41 ms2, P = 0.003; amplitude of the respiration-to-heart rate impulse response decreased from 31.6 to 14.4 ms ⋅ ml−1 ⋅ s−1, P = 0.03; and LF/HF increased from 1.96 to 5.22, P = 0.005). We concluded from this study that the effects of standing were an observed reduction in vagal influence on the heart rate variability of the R-R interval and maintenance of lung volume-related vagal modulation of the P-R and R-T intervals.
Extracellular serotonin changes in VLM during muscle contraction: effects of 5-HT1A-receptor activation
Authors: Asmundsson Gudbjorn , Caringi Daryl , Mokler David J. , Kobayashi Toshio , Ishide Takeshi , Ally Ahmmed
Published: December 2017

This study determined whether muscle contraction causes an increase in extracellular levels of serotonin (5-HT) in the rostral (rVLM) or caudal ventrolateral medulla (cVLM) in anesthetized rats. Muscle contraction, evoked by tibial nerve stimulation, increased mean arterial blood pressure (MAP) by 27 ± 4 mmHg ( n = 8). In addition, 5-HT levels in the rVLM were elevated by 65 ± 9% during the contraction ( n = 8). Results were similar over two repeated contractions. In contrast, muscle contraction increased MAP, but not 5-HT, levels in the cVLM ( n = 6). Tibial nerve stimulation after muscle paralysis had no effect on either MAP or 5-HT levels in both rVLM and cVLM. Microdialysis of a 5-HT1A agonist, 8-OH-DPAT (10 mM), into the rVLM for 30 min ( n = 6) blunted the MAP change and reduced 5-HT release during contraction. Administration of NAN-190, a 5-HT1A antagonist, into the rVLM had no effect on 5-HT release and cardiovascular responses during muscle contraction and blocked the changes in 5-HT, MAP, and heart rate to static contraction after subsequent microdialysis of 8-OH-DPAT. Results demonstrate that 5-HT levels in the rVLM increase during muscle contraction and that 5-HT1A-receptor activation in the rVLM blunts MAP response to muscle contraction via a decrease in the extracellular concentration of 5-HT.
Beat-to-beat estimation of windkessel model parameters in conscious rats
Authors: Molino Paola , Cerutti Catherine , Julien Claude , Cuisinaud Guy , Gustin Marie-Paule , Paultre Christian
Published: December 2017

A windkessel model was applied on a beat-to-beat basis to evaluate the arterial mechanical characteristics in seven conscious rats. Ascending aortic arterial pressure (AP) and blood flow were recorded during steady-state in basal conditions, during infusions of isoprenaline, sodium nitroprusside, and phenylephrine, and after intravenous atenolol injection. For each cardiac cycle the exponential decay time constant (τ) was estimated from the aortic AP curve, peripheral resistances ( R) were taken as the ratio of mean AP to cardiac output, and systemic arterial compliance ( C) was calculated as τ/ R. In all conditions, mean correlation coefficients of the exponential regression and ∼70% of values in each rat were >0.99, demonstrating the model validity. In all conditions τ and C exhibited a large spontaneous variability over time, and beat-to-beat correlations were high between τ and C (0.83 ± 0.03). C was increased by sodium nitroprusside, decreased by isoprenaline, but not significantly decreased by phenylephrine [5.1 ± 0.2, 3.2 ± 0.3, and 3.9 ± 0.2 μl/mmHg, respectively, vs. 4.2 ± 0.3 μl/mmHg (baseline)]. In conclusion, the windkessel model enables τ and C to be reliably estimated in conscious rats during spontaneous and drug-induced hemodynamic variations.
Endothelial and smooth muscle cell conduction in arterioles controlling blood flow
Authors: Welsh Donald G. , Segal Steven S.
Published: December 2017

We performed intracellular recording with Lucifer yellow dye microinjection to investigate the cellular pathway(s) by which constriction and dilation are conducted along the wall of arterioles (diameter 47 ± 1 μm, n = 63) supplying blood flow to the cheek pouch of anesthetized hamsters. At rest, membrane potential ( E m) of endothelial (−36 ± 1 mV) and smooth muscle (−35 ± 1 mV) cells was not different. Micropipette delivery of norepinephrine (NE) or phenylephrine (PE) produced smooth muscle cell depolarization (5–41 mV) and vasoconstriction (7–49 μm) at the site of release and along the arteriole with no effect on E m of endothelial cells. KCl produced conduction of depolarization and vasoconstriction with similar electrical kinetics in endothelial and smooth muscle cells. Acetylcholine triggered conduction of vasodilation (2–25 μm) and hyperpolarization (3–33 mV) along both cell layers; in smooth muscle, this change in E m was prolonged and followed by a transient depolarization. These cell-specific electrophysiological recordings uniquely illustrate that depolarization and constriction are initiated and conducted along smooth muscle, independent of the endothelium. Furthermore, conduction of vasodilation is explained by the spread of hyperpolarization along homologously coupled endothelial and smooth muscle cells, with distinctive responses between cell layers. The discontinuity between endothelium and smooth muscle indicates that these respective pathways are not electrically coupled during blood flow control.
Postjunctional α2-adrenoceptors are not present in proximal arterioles of rat intestine
Authors: Nase Geoffrey P. , Boegehold Matthew A.
Published: December 2017

The purpose of this study was to evaluate two potential stimuli for nitric oxide (NO) release in rat intestinal arterioles during sympathetic nerve activation. To determine whether these vessels contain endothelial α2-adrenoceptors linked to thel-arginine-NO pathway, intravital microscopy was used to study the response of first-order arterioles (1As, 20–40 μm ID) to direct application of 1) the selective α2-agonist BHT-933 and 2) norepinephrine (NE) or sympathetic nerve stimulation before and after α1- or α2-receptor blockade. The effect of sympathetic nerve stimulation on 1A wall shear rate (WSR) was also determined to evaluate the possibility of hemodynamic shear stress as a stimulus for NO release. BHT-933 had no effect on 1A diameter, whereas NE produced dose-dependent constrictions of 5 ± 3 to 15 ± 3 μm, which were usually abolished by the α1-antagonist prazosin but unaffected by the α2-antagonist idazoxan. Sympathetic nerve stimulation at 3, 8, and 16 Hz induced constrictions of 4 ± 1, 8 ± 2, and 17 ± 4 μm, respectively, and these constrictions were also usually abolished by prazosin but unaffected by idazoxan. Resting WSR averaged 1,997 ± 163 s−1and decreased to 1,587 ± 209, 1,087 ± 195, and 537 ± 99 s−1during 3-, 8-, and 16-Hz nerve stimulation. These results suggest that α2-adrenoceptor-dependent pathways do not influence either resting tone or sympathetic constriction of proximal arterioles in the intestinal submucosa and that luminal shear stress in these vessels significantly decreases with sympathetic constriction. It therefore appears unlikely that either α2-receptor activation or changes in hemodynamic shear serve as stimuli for arteriolar NO release during periods of increased sympathetic nerve activity.
Arginase modulates nitric oxide production in activated macrophages
Authors: Chang Chiung-I , Liao James C. , Kuo Lih
Published: December 2017

In macrophages and many other cell types,l-arginine is used as a substrate by both nitric oxide synthase (NOS) and arginase to produce nitric oxide (NO) and urea, respectively. Because the availability ofl-arginine is a major determinant for NO synthesis in the activated macrophage, we hypothesized that NO production may be reduced by arginase via depleting the common substrate in this cell type. To test this hypothesis, we investigated the effect of an arginase inhibitor,l-norvaline, on NO production in J774A.1 mouse macrophages activated by lipopolysaccharide (LPS, 1.0 μg/ml) for 22 h. In the absence of LPS, macrophages produced a low level of NO. In contrast, NO production from these cells was significantly increased in the presence of LPS. Increasing extracellular levels ofl-arginine (0.01–0.8 mM) produced a concomitant increase in NO production of activated macrophages. l-Norvaline (10 mM), which specifically inhibits arginase activity (i.e., reducing urea production by 50%) without altering NOS activity, enhanced NO production (by 55%) from activated macrophages. The enhancement of NO production by l-norvaline was inversely related to the extracellular level ofl-arginine. A more pronounced increase in NO production was observed at the lower level of extracellular l-arginine, i.e., a 55 vs. 28% increase for 0.05 and 0.1 mM extracellularl-arginine, respectively. When the l-arginine concentration exceeded 0.5 mM, thel-norvaline effect was abolished. These results indicate that arginase can compete with NOS for their common substrate and thus inhibit NO production. This regulatory mechanism may be particularly important when the extracellular supply ofl-arginine is limited.
N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor
Authors: Pratt Phillip F. , Hillard Cecilia J. , Edgemond William S. , Campbell William B.
Published: December 2017

It has been reported that the endogenous cannabinoid N-arachidonylethanolamide (AEA), commonly referred to as anandamide, has the characteristics of an endothelium-derived hyperpolarizing factor in rat mesenteric artery. We have carried out studies to determine whether AEA affects coronary vascular tone. The vasorelaxant effects of AEA were determined in isolated bovine coronary artery rings precontracted with U-46619 (3 × 10−9 M). AEA decreased isometric tension, producing a maximal relaxation of 51 ± 9% at a concentration of 10−5 M. Endothelium-denuded coronary arteries were not significantly affected by AEA. The CB1 receptor antagonist SR-141716A (10−6 M) failed to reduce the vasodilatory effects of AEA, suggesting that the CB1 receptor is not involved in this action of AEA. Because AEA is rapidly converted to arachidonic acid and ethanolamine in brain and liver by a fatty acid amide hydrolase (FAAH), we hypothesized that the vasodilatory effect of AEA results from its hydrolysis to arachidonic acid followed by enzymatic conversion to vasodilatory eicosanoids. In support of this hypothesis, bovine coronary arteries incubated with [3H]AEA for 30 min hydrolyzed 15% of added substrate; ∼9% of the radiolabeled product was free arachidonic acid, and 6% comigrated with the prostaglandins (PGs) and epoxyeicosatrienoic acids (EETs). A similar result was obtained in cultured bovine coronary endothelial cells. Inhibition of the FAAH with diazomethylarachidonyl ketone blocked both the metabolism of [3H]AEA and the relaxations to AEA. Whole vessel and cultured endothelial cells prelabeled with [3H]arachidonic acid synthesized [3H]PGs and [3H]EETs, but not [3H]AEA, in response to A-23187. Furthermore, SR-141716A attenuated A-23187-stimulated release of [3H]arachidonic acid, suggesting that it may have actions other than inhibition of CB1 receptor. These experiments suggest that AEA produces endothelium-dependent vasorelaxation as a result of its catabolism to arachidonic acid followed by conversion to vasodilatory eicosanoids such as prostacyclin or the EETs.
Defibrillation depresses heart sarcoplasmic reticulum calcium pump: a mechanism of postshock dysfunction
Authors: Jones Douglas L. , Narayanan Njanoor
Published: December 2017

Presently, the only therapy for ventricular fibrillation is delivery of high-voltage shocks. Despite “successful defibrillation,” patients may have poor cardiac contractility, the mechanisms of which are unknown. Intracellular Ca2+handling by the sarcoplasmic reticulum (SR) plays a major role in contractility. We tested the hypothesis that defibrillation shocks interfere with Ca2+transport function of cardiac SR. Rats anesthetized with pentobarbital sodium had bilateral electrodes implanted subcutaneously for transthoracic shocks. A series of 10 shocks, 10 s apart, at 0–250 V was delivered from a trapezoidal defibrillator. The hearts were rapidly removed, SR-enriched membrane vesicles were isolated, and ATP-dependent Ca2+uptake and Ca2+-stimulated ATP hydrolysis were determined. There was a marked, shock-related decline in Ca2+uptake, whereas adenosinetriphosphatase activity remained unaltered. The polypeptide compositions were similar in control and shocked SR. In Langendorff hearts, shocks also decreased contractility and slowed relaxation. These data indicate that shocks with current densities similar to defibrillation depress Ca2+-pumping function of cardiac SR because of uncoupling of ATP hydrolysis and Ca2+transport. Shock-induced impairment of Ca2+pump function may underlie postshock myocardial dysfunction.
A model for red blood cell motion in glycocalyx-lined capillaries
Authors: Secomb T. W. , Hsu R. , Pries A. R.
Published: December 2017

The interior surfaces of capillaries are lined with a layer (glycocalyx) of macromolecules bound or adsorbed to the endothelium. Here, a theoretical model is used to analyze the effects of the glycocalyx on hematocrit and resistance to blood flow in capillaries. The glycocalyx is represented as a porous layer that resists penetration by red blood cells. Axisymmetric red blood cell shapes are assumed, and effects of cell membrane shear elasticity are included. Lubrication theory is used to compute the flow of plasma around the cell and within the glycocalyx. The effects of the glycocalyx on tube hematocrit (Fahraeus effect) and on flow resistance are predicted as functions of the width and hydraulic resistivity of the layer. A layer of width 1 μm and resistivity 108dyn ⋅ s/cm4leads to a relative apparent viscosity of ∼10 in a 6-μm capillary at discharge hematocrit 45% and flow velocity of ∼1 mm/s. This is consistent with experimental observations of increased flow resistance in microvessels in vivo, relative to glass tubes with the same diameters.
Cerebellar stimulation reduces inducible nitric oxide synthase expression and protects brain from ischemia
Authors: Galea Elena , Golanov Eugene V. , Feinstein Douglas L. , Kobylarz Keith A. , Glickstein Sara B. , Reis Donald J.
Published: December 2017

A focal infarction produced by occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats induced expression of inducible nitric oxide synthase (iNOS) mRNA, measured by competitive reverse transcription-polymerase chain reaction. The mRNA appeared simultaneously in the ischemic core and penumbra at 8 h, peaked between 14 and 24 h, and disappeared by 48 h. At 24 h, inducible nitric oxide synthase (iNOS)-like immunoreactivity was present in the endothelium of cerebral microvessels and in scattered cells, probably representing leukocytes or activated microglia. Electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h, 48 h before MCAO, reduced infarct volumes by 45% by decreasing cellular death in the ischemic penumbra. It also reduced by >90% the expression of iNOS mRNA and protein in the penumbra, but not core, and decreased by 44% the iNOS enzyme activity. We conclude that excitation of neuronal networks represented in the cerebellum elicits a conditioned central neurogenic neuroprotection associated with the downregulation of iNOS mRNA and protein. This neuroimmune interaction may, by blocking the expression of iNOS, contribute to neuroprotection.
Effect of K ATP + channel inhibition on total and regional vascular resistance in guinea pig pregnancy
Authors: Keyes Linda , Rodman David M. , Curran-Everett Douglas , Morris Kenneth , Moore Lorna G.
Published: December 2017

Decreased vascular resistance and vasoconstrictor response during pregnancy enables an increase in cardiac output and regional blood flow to the uterine circulation. We sought to determine whether inhibition of vascular smooth muscle ATP-sensitive potassium ([Formula: see text]) channel activity during pregnancy increased systemic and/or regional vascular resistance and resistance response to ANG II. A total of 32 catheterized, awake, pregnant or nonpregnant guinea pigs were treated with either the [Formula: see text]channel inhibitor glibenclamide (3.5 mg/kg) or vehicle (DMSO) ( n = 8/group). In nonpregnant and pregnant animals, glibenclamide raised blood pressure and systemic, uterine, and coronary vascular resistance, diminishing cardiac output and organ blood flow. Glibenclamide produced a greater rise in coronary vascular resistance in the pregnant than nonpregnant groups and increased renal and cerebral vascular resistance in the pregnant animals only. ANG II infusion raised blood pressure and systemic and renal vascular resistance and lowered cardiac output and renal blood flow in vehicle-treated animals. Glibenclamide augmented ANG II-induced systemic vasoconstriction in the nonpregnant and pregnant groups and the rise in uteroplacental vascular resistance in the pregnant animals. We concluded that [Formula: see text] channel activity likely modulates systemic, uterine, and coronary vascular resistance and opposes ANG II-induced systemic vasoconstriction in nonpregnant and pregnant guinea pigs. Pregnancy augments[Formula: see text] channel activity in the uterine, coronary, renal, and cerebral vascular beds and the uteroplacental circulation during ANG II infusion. Thus increased[Formula: see text] channel activity appears to influence regional control of vascular resistance during guinea pig pregnancy but cannot account for the characteristic decrease in systemic vascular resistance and ANG II-induced systemic vasoconstrictor response.
Mechanics of intraventricular filling: study of LV early diastolic pressure gradients and flow velocities
Authors: Smiseth Otto A. , Steine Kjetil , Sandbæk Gunnar , Stugaard Marie , Gjølberg Tor Ø.
Published: December 2017

This study investigates mechanisms of left ventricular (LV) intracavitary flow during early, rapid filling. In eight coronary artery disease patients with normal LV ejection fraction we recorded simultaneous LV apical and outflow tract pressures and intraventricular flow velocities by color M-mode Doppler echocardiography. In five anesthetized dogs we also recorded left atrial pressure and LV volume by sonomicrometry. In patients, as the early diastolic mitral-to-apical filling wave arrived at the apex, we observed an apex-outflow tract pressure gradient of 3.5 ± 0.3 mmHg (mean ± SE). This pressure gradient correlated with peak early apex-to-outflow tract flow velocity ( r = 0.75, P < 0.05). The gradient was reproduced in the dog model and decreased from 3.1 ± 0.3 to 1.7 ± 0.5 mmHg ( P < 0.05) with caval constriction and increased to 4.2 ± 0.5 mmHg ( P < 0.001) with volume loading. The pressure gradient correlated with peak early transmitral flow (expressed as time derivative of LV volume; r = 0.95) and stroke volume ( r = 0.97). In conclusion, arrival of the early LV filling wave at the apex was associated with a substantial pressure gradient between apex and outflow tract. The pressure gradient was sensitive to changes in preload and correlated strongly with peak early transmitral flow. The significance of this gradient for intraventricular flow propagation in the normal and the diseased heart remains to be determined.
Segmental effect of spinal NK-1 receptor blockade on the pressor reflex
Authors: Wilson L. Britt , Hand Gregory A.
Published: December 2017

The physiological effects of substance P (SP) are mediated via activation of neurokinin-1 (NK-1) receptors. The purpose of this study was to test the hypothesis that blockade of NK-1 receptors in the dorsal horn, both at the site of entry for the primary afferent neurons and adjacent spinal segments, attenuates the pressor reflex evoked by static contraction and stretch of skeletal muscle. Cats were anesthetized with α-chloralose and urethan, and a laminectomy was performed. With the exception of the L7 dorsal root, the dorsal and ventral roots from L5 to S2 were sectioned on one side of the spinal cord. Thus the primary afferent fibers mediating the pressor reflex enter the spinal cord via the L7 dorsal root in these experiments. Based on dose-response data, dialysis of the NK-1 receptor antagonist CP-96,345 (5 mM for 2 h) into the L7 dorsal horn ipsilateral to the contracting muscle attenuated the pressor response to static contraction (75 ± 15 vs. 46 ± 7 mmHg; n = 5 cats) but not muscle stretch (60 ± 12 vs. 50 ± 8 mmHg). Administration of the inactive enantiomer of CP-96,345, CP-96,344 (5 mM for 2 h), into the L7 dorsal horn failed to alter the cardiovascular changes elicited by contraction (45 ± 7 vs. 43 ± 6 mmHg) and stretch (31 ± 8 vs. 32 ± 11). Dialysis of 5 mM CP-96,345 into the dorsal horn at the L6 and S1 segments for 2 h decreased the peak pressor response to static contraction (58 ± 9 vs. 31 ± 6 mmHg; n = 7) and muscle stretch (61 ± 6 vs. 44 ± 8 mmHg). These data suggest that the activation of NK-1 receptors, both at the site of entry and in regions outside of the entry site for afferent neurons, is involved in the spinal processing that produces the pressor reflex evoked by static contraction of skeletal muscle.
Relationship among NO, the KATP channel, and opioids in hypoxic pial artery dilation
Authors: Armstead William M.
Published: December 2017

Nitric oxide (NO), opioids, and ATP-sensitive K+(KATP) channel activation contribute to hypoxia-induced pial artery dilation. NO releasers and cGMP analogs increase opioid concentration in cerebrospinal fluid (CSF) and elicit dilation via KATPchannel activation. Opioids themselves also elicit dilation via KATP channel activation. This study was designed to investigate the relationships among the above mechanisms in hypoxic pial artery dilation using newborn pigs equipped with a closed cranial window. Cromakalim (10−8 and 10−6 M), a KATP agonist, produced dilation that was unchanged by the NO synthase inhibitor N-nitro-l-arginine (l-NNA, 10−6 and 10−3 M): 13 ± 1 and 31 ± 1 vs. 14 ± 1 and 31 ± 1% before and after 10−3 Ml-NNA. Cromakalim dilation also was not associated with increased CSF cGMP and was unchanged by the Rp diastereomer of 8-bromoguanosine 3′,5′-cyclic monophosphothioate, a cGMP antagonist. Glibenclamide (10−6 M), a KATP antagonist, attenuated hypoxic dilation but hypoxia-associated CSF cGMP release was unchanged: 457 ± 12 and 935 ± 30 vs. 458 ± 11 and 921 ± 22 fmol/ml. Coadministration ofl-NNA with glibenclamide had no further effect on the already diminished hypoxic dilation but blocked the hypoxia-associated rise in CSF cGMP. Cromakalim had no effect on CSF methionine enkephalin: 1,012 ± 28 and 1,062 ± 32 pg/ml. These data show that KATP channel agonists do not elicit dilation via NO/cGMP and do not release opioids. NO release during hypoxia also is independent of KATP channel activation. These data suggest that hypoxic dilation results from the sequential release of NO, cGMP, and opioids, which in turn activate the KATP channel.
Kinetics of Vascular and Extravascular Protein Exchange in Unbled and Bled Dogs
Authors: Wasserman Karlman , Joseph Jeanne D. , Mayerson H. S.
Published: December 2017

Unanesthetized, healthy greyhounds were infused with 25% albumin or bled, injected with I131-labeled albumin and albumin specific activities determined. It is shown that the albumin specific activity curves can be altered by changing the ratio of the vascular to extravascular albumin masses in a manner predicted from the mathematics of a two-compartment system. Increase of vascular albumin mass relative to extravascular mass results in a smaller initial disappearance of albumin specific activity from the blood stream and a faster approach to equilibrium. Decrease of vascular albumin mass relative to extravascular mass by bleeding shows that 50% of albumin replacement after hemorrhage appears to be accomplished within 24 hours. Almost all of this protein comes from the extravascular compartment. Rapid anabolism accounts for the replenishment of protein for the next 2–5 days, during and after which there is a reduced catabolism of the existing plasma albumin. The results indicate that an extravascular albumin mass exists as a separate entity and net movements may occur from this mass into the plasma when the equilibrium between the vascular and extravascular masses is disturbed.
Inability of Cerebrospinal Fluid to Nourish the Spinal Cord
Authors: Wolff Peter H. , Tschirgi Robert D.
Published: December 2017

Cephalad perfusion with Tyrode's solution of the spinal subarachnoid space between a lumbar and cisternal tap in anesthetized cats had no effect on spinal reflexes, respiration or pupillary size for periods of 8 hours. Alteration of Ca++ or K+ concentration in the perfusate produced immediate changes in these indices, indicating the availability of the perfusate to neural elements. The onset and course of patellar areflexia, respiratory depression and pupillary dilatation resulting from i.v. insulin-induced hypoglycemia could not be influenced by including high concentrations of glucose, glutamate, succinate or a combination of these latter two in the subarachnoid perfusate. It is concluded that the cerebrospinal fluid cannot act as a sufficient medium for transport from the blood of nutrient substrates essential for maintaining function in the central nervous system.
Renal Tubular Reabsorption of Acetoacetate, Inorganic Sulfate and Inorganic Phosphate in the Dog as Affected by Glucose and Phlorizin
Authors: Cohen Julius J. , Berglund Fredrik , Lotspeich William D.
Published: December 2017

The effects of glucose and phlorizin on the maximal reabsorptive rates of acetoacetate, sulfate and phosphate were studied in the dog. Increased rates of glucose reabsorption depress maximal acetoacetate, sulfate and phosphate transport. Phlorizin not only reverses this depressant effect of glucose on these three ions, but actually raises their maximal reabsorptive rates above those of the control levels. These findings for acetoacetate and sulfate reabsorption are similar to those previously reported for phosphate reabsorption. The three ions, acetoacetate, sulfate and phosphate share a common reaction with glucose during their tubular transport. Glucose is the predominant compound, depressing any of the other three ions after they have reached maximal reabsorptive rates. The possible implications of these phenomena in the general problem of tubular transport are discussed.
Arterial Pressure Response to Infused Serotonin in Normotensive Dogs, Cats, Hypertensive Dogs and Man
Authors: Page Irvine H. , McCubbin J. W.
Published: December 2017

Arterial pressure response to intravenous infusion of serotonin in dogs and cats is usually a sustained fall; this differs from the usual response to a single quick injection of serotonin and suggests that the mechanisms controlling response are different depending upon the manner of administration of the drug. It is concluded that when serotonin is infused the depressor response has at least three main contributory mechanisms: a) release of endogenous histamine by serotonin; b) peripheral inhibition of neurogenic vasoconstriction; c) a dose-response relationship that, in some preparations, determines whether change in arterial pressure shall be a rise or fall. The response to intravenous infusion of serotonin in three hypertensive patients was different from that in normotensive dogs and cats or neurogenic hypertensive dogs. These patients responded with a small, sustained rise in arterial pressure. Infusion of either histamine or serotonin in dogs caused similar changes in response to other drugs: those to DMPP were strikingly augmented and those to noradrenaline were moderately increased in both dogs and cats. Responses to angiotonin, barium chloride, and Aramine were essentially unchanged. The depressor action of the histamine releasing drug, 48/80, or histamine, was sharply reduced or abolished.
Spreading Depression in Rabbit, Cat and Monkey
Authors: Harreveld A. Van , Stamm J. S. , Christensen Eleanor
Published: December 2017

Rabbits, cats and monkeys show species difference in the consistency and frequency with which spreading depression (SD) can be elicited during the first hours after exposure of the cortex. In the rabbit SD can be produced consistently at 6–10-minute intervals. In most of the preparations of the cat it is also possible to produce a series of SDs when using a longer interval (15–20 min.) between stimulations. Only rarely is it possible to obtain in the monkey a series of SDs even when long intervals are interjected between stimuli. However, the majority of preparations responded at least once with a SD. It has been possible to lead off SD in rabbits and cats with extradural electrodes implanted in the skull 5–7 days earlier. These electrodes were in most instances flush with the dural surface of the skull, resting on the undamaged dura. In the rabbit photo-Metrazol stimulation can produce SD which also has been recorded with the implanted electrodes. Since there is no reason to believe that the cortex in these latter experiments was damaged or in any other way abnormal, the conclusion was drawn that normal cortex can exhibit spreading depression.
Intracellular Slow Potential of Dorsal Root Fibers
Authors: Koketsu K.
Published: December 2017

Intracellular potential changes associated with excitation were recorded from a dorsal root fiber in the funiculus of an isolated spinal cord of a bullfrog or toad. The spike potential of a dorsal root fiber was observed to follow the slow positive (inside) potential. This slow potential was recorded without a spike potential by applying stimuli sub-threshold for the impaled nerve fiber. The size of the slow potential increased gradually with increased strength of dorsal root stimuli, but with no accompanying prolongation of its declining phase. Dorsal root reflex discharges were occasionally superimposed on this slow potential. No summation of the slow potential resulted from two successive supramaximal stimuli. The slow potential induced by a test stimulus showed considerable occlusion even half a second after the conditioning stimulus. The slow positive (inside) potential was also recorded intracellularly by applying antidromic ventral root stimuli. The slow potential recorded here proved to be generated intrinsically by the depolarization of the surface membrane of the impaled nerve fiber. Active depolarization of the membrane of the terminal endings of the dorsal root fiber may spread out electrotonically along the membrane of the nerve fiber and provide this slow potential. The membrane of terminal endings of a single dorsal root fiber may be depolarized secondarily by the activity of other dorsal root fibers or secondary neurons. The relationship between positive deflection of the cord dorsum potential, the dorsal root potential, and the slow potential recorded intracellularly in this experiment has been analyzed.
In Vitro Effects of Acetate Ion on Renal Metabolism of p-Aminohippurate
Authors: Despopoulos Agamemnon
Published: December 2017

Renal cortical slices from four strains of rats were incubated with p-aminohippurate (PAH) and the concentration gradient for PAH (S/M PAH) was determined. Acetate ion (Ac) at a concentration of 0.01 m failed to induce the expected increase in S/M PAH. At larger concentrations of Ac, the S/M PAH was depressed. Maximal depression occurred when the concentration of Ac was 0.1 m. Ac produced a concurrent increase in the respiratory rate, an increase in the terminal tissue weight, and no significant alteration of the rate of N-acetylation of PAH.
Rhinencephalon and Behavior
Authors: Schreiner Leon , Kling Arthur
Published: December 2017

Lesions of the rhinencephalon, primarily restricted to the amygdaloid complex, modify aggressive behavior of lynxes ( Lynx rufus), agoutis ( Dasyprocta agouti), monkeys ( Macacus rhesus) and domestic cats toward relative docility and precipitate a state of chronic hypersexuality. Relative docility was characterized by failure of the experimental animals to exhibit aggressive behavior, fear, or escape activity in the presence of threatening situations which precipitated such behavior in their preoperative periods. Hypersexuality was exhibited by marked increases in copulatory activity with males and females of their own and other animal species. It is concluded that the rhinencephalon and its diencephalic connections, in association with endocrine systems, are important regulators of emotional and sexual behavior of rodents, carnivores and primates.
Effects of Complete Ureteral Obstruction in Dogs on Kidney Function
Authors: Kerr Walter S.
Published: December 2017

Effects of complete ureteral obstruction for 7, 14, 21 and 28 days on renal function, and the degree and rate of recovery following release of the obstruction were studied by renal clearance methods in dogs. On the day of release of the ureter the rate of flow from the previously obstructed kidney was sufficient to measure accurately clearances only in dogs with ureteral obstruction of 1 and 2 weeks. One hour after release, the GFR and ERPF in the dogs obstructed 2 weeks were significantly less than in those obstructed for 1 week. Subsequently, renal clearance tests were made at intervals of 1 week until maximum recovery was observed. The dogs obstructed for 1 week showed the greatest improvements in GFR and ERPF and the dog obstructed for 4 weeks showed the least improvement. The control (left) kidney was removed from five dogs 2 days after release of the right ureter. The removal of the control kidney resulted in a more prompt and greater increase of GFR and ERPF and a prompt increase in the rate of urine formation by the previously obstructed kidney in all groups. Removal of the contralateral kidney in the three dogs obstructed 2, 3 and 4 weeks caused an elevation of the NPN which never returned to normal. The ability of the previously obstructed kidney in all the groups to concentrate urine was impaired. Ability to dilute urine or to produce an alkaline and acid urine was not impaired. In three dogs the contralateral kidney was removed a number of days after maximum recovery was noted. In each case renal clearances increased, demonstrating that even after long periods of stabilization (approximately 2 years in one dog) these kidneys could still be stimulated to increase the GFR and ERPF.
Water Balance of the Camel
Authors: Schmidt-Nielsen Bodil , Schmidt-Nielsen Knut , Houpt T. R. , Jarnum S. A.
Published: December 2017

Camels ( Camelus dromedarius) were exposed to prolonged periods of water deprivation during winter, spring and summer in the Sahara desert. Determinations were made of: weight changes, water and food intake, urine flow and concentrations, plasma concentrations, etc. It was found that the camel can tolerate a loss of water corresponding to 30% of its body weight even when exposed to the severe desert heat. Other mammals dehydrated in a hot environment may die from circulatory failure already when the water loss involves 12% of the body weight. Unlike many other mammals the camel does not lose its appetite when deprived of water but continues to eat normally until the desiccation becomes very severe. It has a low urine output (0.5–1 l/day when kept on a diet of dates and hay), a low water content in the feces, and, when dehydrated in the summer, a very low evaporative water loss. When offered water the camel drinks in 10 minutes enough water for complete rehydration. The longest period that we kept a camel on dry food without drinking water in the hot summer was 17 days. This camel was not working and it had its protective fur which decreased the heat gain from the environment. It is concluded that the ability of the camel to withstand prolonged dehydration is due to: a) tolerance to an extremely high degree of desiccation of the body and b) low overall water expenditure. Particularly effective as a water conserving mechanism is the low evaporative water loss during dehydration in the summer.