bluuebunny/crossref_metadata_2025 huggingface dataset:
Smoking impairs baroreflex sensitivity in humans
Authors: Mancia G. , Groppelli A. , Di Rienzo M. , Castiglioni P. , Parati G.
Published: December 2017

In 10 healthy smokers, finger blood pressure was recorded continuously for 1 h in a supine control condition and for 1 h while smoking four cigarettes, one every 15 min. Smoking increased average systolic blood pressure (+19%, P < 0.01) and its variability and reduced pulse interval (reciprocal of heart rate, -22%, P < 0.01) and its variability. Baroreflex sensitivity, as assessed by the slope of spontaneous hypertension/bradycardia or hypotension/tachycardia sequences and by the alpha-coefficient (squared ratio between pulse interval and systolic blood pressure spectral powers at 0.1 Hz) was significantly decreased (P < 0.01) during smoking, whereas there were no effects of smoking on the reflex changes in pulse interval induced by carotid baroreceptor stimulation through a neck suction device. Sham smoking by a drinking straw had no effects on any of the above parameters. Thus, when assessed in the absence of laboratory maneuvers in daily life conditions, baroreflex sensitivity is markedly impaired by smoking. This impairment may contribute to the smoking-induced increase in blood pressure and heart rate as well as to the concomitant alterations in their variability.
β-Adrenoceptors in vascular capacitance responses to unloading of carotid baroreceptors in anesthetized dogs
Authors: Karim F. , Poucher S. M.
Published: December 2017

The role of β- and α-adrenoceptors in the total vascular capacitance responses to changing pressure in vascularly isolated carotid sinuses of anesthetized and atropinized dogs was investigated. A change in vascular capacitance was determined by measuring the shift of blood in and out of a reservoir that was connected to the aorta and maintained at a constant pressure. Changes in carotid sinus pressure from 135 to 57 mmHg and back to 137 mmHg resulted in a rapid vascular capacitance response of ∼30 ml in the absence of adrenoceptor antagonists. Administration of a β2-adrenoceptor antagonist (ICI-118551) caused a significant enhancement of the capacitance responses to similar decreases and increases in carotid sinus pressure (∼130%). Administration of a β1-adrenoceptor antagonist (CGP-20712A) did not cause any further enhancement of the responses. However, an α-blocker (phentolamine) reduced the responses by 75%. The results suggest that in the presence of a β2-adrenoceptor antagonist vascular capacitance responses to loading and unloading of baroreceptors are greatly enhanced and that patients suffering from orthostatic syncope may benefit from this kind of drug.
LPS induces late cardiac functional protection against ischemia independent of cardiac and circulating TNF-α
Authors: Meng Xianzhong , Ao Lihua , Brown James M. , Meldrum Daniel R. , Sheridan Brett C. , Cain Brian S. , Banerjee Anirban , Harken Alden H.
Published: December 2017

Lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α independently induce cardioprotection against ischemia in the rat at 24 h after administration, suggesting that endogenously synthesized TNF-α may play a role in LPS-induced protection. The purposes of this study were 1) to delineate the time course of LPS-induced cardiac functional protection against ischemia and its relation with myocardial and circulating TNF-α profile, 2) to examine whether prior protein synthesis inhibition abrogates the protection, and 3) to assess the effects of TNF-α inhibition and neutralization on the protection. Rats were treated with LPS (0.5 mg/kg ip). Cardiac functional resistance to normothermic global ischemia-reperfusion was examined at sequential time points after LPS treatment in isolated hearts by the Langendorff technique. Myocardial and circulating TNF-α was determined by enzyme-linked immunosorbent assay at 1–24 h after LPS treatment. Protection was apparent at 24 h, 3 days, and 7 days but not at 2 or 12 h. Maximal protection at 3 days was abolished by cycloheximide pretreatment (0.5 mg/kg ip 3 h before LPS treatment). Increases in myocardial and circulating TNF-α preceded the acquisition of protection. Dexamethasone pretreatment (4.0 or 8.0 mg/kg ip 30 min before LPS treatment) abolished peak increase in myocardial TNF-α and substantially suppressed circulating TNF-α (54.3 and 85.9% inhibition, respectively) without an influence on the maximal protection. Similarly, maximal protection was not affected by TNF binding protein (40 or 80 μg/kg iv immediately after LPS treatment). The results suggest that LPS-induced cardiac functional protection against ischemia is a delayed and long-lasting protective response that may involve de novo protein synthesis. Although LPS-induced increase in myocardial and circulating TNF-α precedes the delayed protection, it may not be required for the delayed protection.
Regulation of endometrial blood flow in ovariectomized rats: assessment of the role of nitric oxide
Authors: Zhang Ren-Sheng , Guth Paul H. , Scremin Oscar U. , Singh Rajan , Pervin Shehla , Chaudhuri Gautam
Published: December 2017

The purpose of this study was to evaluate the role of nitric oxide (NO) in the maintenance of basal endometrial blood flow of ovariectomized rats and in the increase of endometrial blood flow after administration of estradiol 17β (E2β). Endometrial blood flow was repeatedly measured with the H2 gas clearance technique in ovariectomized rats. N ω-nitro-l-arginine methyl ester (l-NAME) dose dependently reduced basal endometrial blood flow and increased mean arterial blood pressure and endometrial vascular resistance. E2β (1 μg/kg iv) increased endometrial blood flow and reduced endometrial vascular resistance, which peaked by 2 h after the injection. The vasoconstrictive activity of l-NAME (an inhibitor for NO synthesis) was compared with that of phenylephrine (PE, an α-receptor agonist acting through an NO-independent mechanism). Doses ofl-NAME (1 and 3 mg/kg iv) were matched with those of PE (3.2 and 6.4 mg ⋅ kg−1 ⋅ h−1iv), as they induced an approximately equivalent percent increase in basal endometrial vascular resistance. The percent increases of endometrial vascular resistance in E2β-treated animals by the two agents in matched doses were also of a similar magnitude. When animals were first treated with l-NAME or PE, E2β lost the ability to reduce endometrial vascular resistance. Enzyme activity and gene expression of NO synthase in the rat uterine tissue were also examined after E2β treatment, and no significant changes were observed. These data raise doubts about the role of NO in the regulation of endometrial blood flow after acute administration of E2β and suggest that other mechanisms may be involved.
Endothelin impairs ATP-sensitive K+ channel function after brain injury
Authors: Kasemsri T. , Armstead W. M.
Published: December 2017

In piglets, pial arteries constrict, ATP-sensitive K+(KATP) channel function is impaired, and cerebrospinal fluid endothelin-1 (ET-1) increases to 10−10 M after brain injury [fluid percussion injury (FPI)]. Nitric oxide (NO) elicits dilation via guanosine 3′,5′-cyclic monophosphate (cGMP) and KATP channel activation. This study was designed to characterize the relationship between ET-1 and impaired function of KATP channels after FPI. Injury was produced via the lateral FPI technique in piglets equipped with a closed cranial window. Cromakalim, a KATP agonist, produced dilation that was attenuated by FPI and partially restored by BQ-123, an ET-1 antagonist (11 ± 1 and 23 ± 2 vs. 2 ± 1 and 4 ± 1 vs. 8 ± 1 and 17 ± 2% for responses to 10−8 and 10−6 M cromakalim before FPI, after FPI, and after FPI with BQ-123, respectively). Because ET-1 constriction may antagonize dilation, separate experiments were conducted under conditions of equivalent baseline diameter in the absence and presence of ET-1 (10−10 M). Cromakalim dilation was attenuated by ET-1 and partially restored by the protein kinase C (PKC) inhibitor staurosporine (12 ± 1 and 28 ± 1 vs. 2 ± 1 and 21 ± 3 vs. 9 ± 1 and 29 ± 2% for 10−8 and 10−6 M cromakalim, cromakalim with ET-1, and cromakalim with ET-1+staurosporine, respectively). Similar interactions were observed with calcitonin gene-related peptide, 8-bromoguanosine 3′,5′-cyclic monophosphate, and the NO releasers sodium nitroprusside and S-nitroso- N-acetylpenicillamine. These data show that ET-1 blunts KATP channel-, NO-, and cGMP-mediated dilation. These data suggest that ET-1 contributes to altered cerebral hemodynamics after FPI through impairment of KATP channel function via PKC activation.
Endogenous histamine stimulates ischemically sensitive abdominal visceral afferents through H1 receptors
Authors: Fu Liang-Wu , Pan Hui-Lin , Longhurst John C.
Published: December 2017

Abdominal ischemia stimulates sympathetic visceral afferents to reflexly activate the cardiovascular system. We have shown previously that topical application of histamine (HA) to the gastric wall causes reflex cardiovascular responses and have documented increased histamine concentrations in intestinal lymph and portal venous plasma during brief abdominal ischemia. In the present study, we hypothesized that histamine produced during ischemia activates ischemically sensitive C-fiber afferents by stimulation of H1 receptors. Nerve activity of single-unit abdominal visceral C-fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats. Injection of histamine (25 μg/kg ia) significantly increased activity of nine ischemically sensitive C fibers from 0.09 ± 0.06 to 1.11 ± 0.20 imp/s. An H1-receptor agonist, 2-(3-chlorophenyl)histamine (250 μg/kg ia), also increased activity of these afferents from 0.11 ± 0.04 to 0.64 ± 0.18 imp/s ( P < 0.05). Furthermore, an H1-receptor antagonist (pyrilamine, 0.2 mg/kg iv) significantly attenuated the increased activity in 11 other C fibers from 0.91 ± 0.16 to 0.35 ± 0.06 imp/s (ischemia vs. pyrilamine + ischemia) and eliminated the response of 9 separate ischemically sensitive afferents to histamine. Conversely, both the H2-receptor agonist dimaprit (500 μg/kg ia) and the H3-receptor agonist ( R)-α-methylhistamine (250 μg/kg ia) did not significantly alter the activity of these nine afferents. In nine separate cats treated with indomethacin (5 mg/kg iv), pyrilamine (0.2 mg/kg iv) further significantly attenuated the increased activity in seven of nine C fibers during ischemia, and indomethacin (5 mg/kg iv) attenuated the response of eight other afferents to histamine. These data suggest that during mesenteric ischemia endogenous histamine contributes to the activation of afferents through direct stimulation of histamine H1 receptors and that histamine’s stimulating effect on these afferents is dependent partially on production of prostaglandins.
Contribution of a voltage-sensitive calcium release mechanism to contraction in cardiac ventricular myocytes
Authors: Howlett Susan E. , Zhu Jie-Quan , Ferrier Gregory R.
Published: December 2017

The contribution of a voltage-sensitive release mechanism (VSRM) for sarcoplasmic reticulum (SR) Ca2+ to contraction was investigated in voltage-clamped ventricular myocytes at 37°C. Na+ current was blocked with lidocaine. The VSRM exhibited steady-state inactivation (half-inactivation voltage: −47.6 mV; slope factor: 4.37 mV). When the VSRM was inactivated, contraction-voltage relationships were proportional to L-type Ca2+current ( I Ca-L). When the VSRM was available, the relationship was sigmoidal, with contractions independent of voltage positive to −20 mV. VSRM and I Ca-Lcontractions could be separated by activation-inactivation properties. VSRM contractions were extremely sensitive to ryanodine, thapsigargin, and conditioning protocols to reduce SR Ca2+ load. I Ca-Lcontractions were less sensitive. When both VSRM and I Ca-L were available, sigmoidal contraction-voltage relationships became bell-shaped with protocols to reduce SR Ca2+ load. Myocytes demonstrated restitution of contraction that was slower than restitution of I Ca-L. Restitution was a property of the VSRM. Thus activation and recovery of the VSRM are important in coupling cardiac contraction to membrane potential, SR Ca2+ load, and activation interval.
Transfer function analysis of dynamic cerebral autoregulation in humans
Authors: Zhang Rong , Zuckerman Julie H. , Giller Cole A. , Levine Benjamin D.
Published: December 2017

To test the hypothesis that spontaneous changes in cerebral blood flow are primarily induced by changes in arterial pressure and that cerebral autoregulation is a frequency-dependent phenomenon, we measured mean arterial pressure in the finger and mean blood flow velocity in the middle cerebral artery (V˙MCA) during supine rest and acute hypotension induced by thigh cuff deflation in 10 healthy subjects. Transfer function gain, phase, and coherence function between changes in arterial pressure andV˙MCA were estimated using the Welch method. The impulse response function, calculated as the inverse Fourier transform of this transfer function, enabled the calculation of transient changes inV˙MCA during acute hypotension, which was compared with the directly measured change in V˙MCA during thigh cuff deflation. Beat-to-beat changes inV˙MCA occurred simultaneously with changes in arterial pressure, and the autospectrum of V˙MCA showed characteristics similar to arterial pressure. Transfer gain increased substantially with increasing frequency from 0.07 to 0.20 Hz in association with a gradual decrease in phase. The coherence function was >0.5 in the frequency range of 0.07–0.30 Hz and <0.5 at <0.07 Hz. Furthermore, the predicted change inV˙MCA was similar to the measuredV˙MCA during thigh cuff deflation. These data suggest that spontaneous changes inV˙MCA that occur at the frequency range of 0.07–0.30 Hz are related strongly to changes in arterial pressure and, furthermore, that short-term regulation of cerebral blood flow in response to changes in arterial pressure can be modeled by a transfer function with the quality of a high-pass filter in the frequency range of 0.07–0.30 Hz.
Extracellular matrix and pulmonary hypertension: control of vascular smooth muscle cell contractility
Authors: Lee Kyung-Mi , Tsai Kenneth Y. , Wang Ning , Ingber Donald E.
Published: December 2017

Pulmonary hypertension is characterized by increased vascular resistance due to smooth muscle cell hyperactivity and excess deposition of extracellular matrix (ECM) in the vessel wall. We investigated the possibility that changes in cell-ECM interactions may play an active role in this process by modifying the contractile response of pulmonary vascular smooth muscle (PVSM) cells. Contractility was measured within individual cultured PVSM cells, when resting or stimulated with vasoactive agents, by quantitating changes in stiffness of the cytoskeleton (CSK) using magnetic twisting cytometry (N. Wang, J. P. Butler, and D. E. Ingber. Science 260: 1124–1127, 1993). Control studies confirmed that changes in CSK stiffness closely paralleled alterations in cell contraction and relaxation as measured in response to endothelin-1 (ET-1) and dibutyryl guanosine 3′,5′-cyclic monophosphate (cGMP), respectively, in a collagen gel contraction assay. CSK stiffness and contractile tone in cultured PVSM cells increased in direct proportion as the density of fibronectin (FN) coating was raised from 10 to 500 ng/well in 96-well plates. Dibutyryl cGMP had no effect in cells on low FN, although it completely inhibited the FN-dependent increase in CSK stiffness on higher ECM densities. In contrast, ET-1 induced the greatest increase in CSK stiffness on the intermediate FN density (100 ng/well). The reduced sensitivity to ET-1 on high FN was not due to dysfunction of the contractile apparatus nor to changes in protein tyrosine phosphorylation. Taken together, these results show that ECM can modulate PVSM cell contractility and suggest that the changes in ECM observed in hypertensive vessels could play an important role in the etiology of this disease.
Preconditioning in rat hearts is independent of mitochondrial F1F0ATPase inhibition
Authors: Green David W. , Murray Holt N. , Sleph Paul G. , Wang Feng-Lai , Baird Anne J. , Rogers W. Lynn , Grover Gary J.
Published: December 2017

Mitochondrial F1F0adenosinetriphosphatase (ATPase) is responsible for the majority of ATP synthesis during normoxic conditions, but under ischemic conditions it accounts for significant ATP hydrolysis. A previous study showed that preconditioning in isolated rat hearts is mediated by inhibition of this ATPase during ischemia. We tested this hypothesis in our isolated rat heart model of preconditioning. Preconditioning was accomplished by three 5-min periods of global ischemia separated by 5 min of reperfusion. This was followed by 20 min of global ischemia and 30 min of reperfusion. Preconditioning significantly enhanced reperfusion contractile function and reduced lactate dehydrogenase release but paradoxically reduced the time to onset of contracture during global ischemia. Myocardial ATP was depleted at a faster rate during the prolonged ischemia in preconditioned than in sham-treated hearts, which is consistent with the reduced time to contracture. ATP during reperfusion was repleted more rapidly in preconditioned hearts, which is consistent with their enhanced contractile function. Preconditioning significantly reduced lactate accumulation during the prolonged ischemia. We were not able to demonstrate that mitochondrial F1F0ATPase (measured in submitochondrial particles) was inhibited by preconditioning before or during the prolonged ischemia. The mitochondrial ATPase inhibitor oligomycin significantly conserved ATP during ischemia and increased the time to the onset of contracture, which is consistent with inhibition of the mitochondrial ATPase. Our results show that preconditioning in rat hearts can be independent of mitochondrial ATPase inhibition as well as ATP conservation.
Controlled breathing protocols probe human autonomic cardiovascular rhythms
Authors: Cooke William H. , Cox James F. , Diedrich André M. , Taylor J. Andrew , Beightol Larry A. , Ames James E. , Hoag Jeffrey B. , Seidel Henrik , Eckberg Dwain L.
Published: December 2017

The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (∼0.5–0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing ( P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2modestly ( P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.
KATP channels are common mediators of ischemic and calcium preconditioning in rabbits
Authors: Kouchi Ichiro , Murakami Tomoyuki , Nawada Ryuzo , Akao Masaharu , Sasayama Shigetake
Published: December 2017

Calcium preconditioning (CPC), like ischemic preconditioning (IPC), reduces myocardial infarct size in dogs and rats. ATP-sensitive potassium (KATP) channels induce cardioprotection of IPC in these animals. To determine whether KATP channels mediate both IPC and CPC, pentobarbital sodium-anesthetized rabbits received 30 min of coronary artery occlusion followed by 180 min of reperfusion. IPC was elicited by 5 min of occlusion and 10 min of reperfusion, and CPC was elicited by two cycles of 5 min of calcium infusion with an interval period of 15 min. Infarct size expressed as a percentage of the area at risk was 38 ± 3% (mean ± SE) in controls. IPC, CPC, and pretreatment with a KATP channel opener, cromakalim, all reduced infarct size to 13 ± 2, 17 ± 2, and 12 ± 3%, respectively ( P < 0.01 vs. controls). Glibenclamide, a KATP channel blocker administered 45 min (but not 20 min) before sustained ischemia, attenuated the effects of IPC and CPC (31 ± 4 and 41 ± 6%, respectively). Thus KATP channel activation appears to contribute to these two types of cardioprotection in rabbits.
Acute and chronic hypokalemia sensitize the isolated heart to hypoxic injury
Authors: Shapiro Joseph I. , Banerjee Anirban , Reiss Oscar K. , Elkins Nancy
Published: December 2017

We examined the effects of acute and/or chronic hypokalemia on responses to 30 min of hypoxia and recovery in the isolated, perfused heart model. We found that both acute hypokalemia and chronic hypokalemia impaired contractility [expressed as maximum slope of pressure increase over time (dP/d t): 501 ± 49 and 529 ± 48 vs. 1,302 ± 118 mmHg/s, P < 0.01] and recovery of ATP concentrations (determined with31P NMR spectroscopy: 30 ± 6 and 40 ± 10 vs. 67 ± 5% initial, P < 0.05) at 30 min of recovery. Moreover, the combination of acute hypokalemia and chronic hypokalemia had additive effects (dP/d t 166 ± 15 mmHg/s and ATP 21 ± 7% initial, both P < 0.01). We also measured cytosolic calcium with surface fluorescence spectroscopy after indo 1 loading. Acute hypokalemia and acute hypokalemia + chronic hypokalemia increased cytosolic calcium (averaged throughout the cardiac cycle) during and after hypoxia (390- to 460-nm ratio at 30 min of recovery: 0.46 ± 0.07 and 0.65 ± 0.07 vs. 0.18 ± 0.03, P < 0.01), whereas control and chronic hypokalemia hearts had only small changes with hypoxia and recovery. Finally, when we examined mitochondria isolated from hearts perfused under experimental conditions, we found that chronic hypokalemia-alone mitochondria and chronic hypokalemia + acute hypokalemia mitochondria had marked impairment of state 3 respiration compared with control hearts (52 ± 13 and 50 ± 9 vs. 128 ± 10 natm ⋅ min−1 ⋅ mg protein−1 with succinate as substrate, P < 0.01), whereas acute hypokalemia mitochondria demonstrated only subtle changes. These data suggest that both acute hypokalemia and chronic hypokalemia impair cardiac responses to hypoxia. The mechanism may involve impairment of calcium metabolism, but cytosolic calcium alterations do not explain all of the metabolic and functional effects of acute hypokalemia and chronic hypokalemia in the setting of hypoxia.
R-R variability detects increases in vagal modulation with phenylephrine infusion
Authors: Bloomfield Daniel M. , Zweibel Steven , Bigger J. Thomas , Steinman Richard C.
Published: December 2017

High-frequency power, measured from power spectral analysis of R-R variability, reflects vagal modulation of the sinus node. Unexpectedly, a recent study reported a decrease in high-frequency power during the infusion of phenylephrine despite a prolongation of R-R intervals, indicating an increase in vagal activity. To better define the limitations of high-frequency power to quantify vagal modulation, we measured high-frequency power during the infusion of phenylephrine (0.4, 0.8, and 1.2 μg ⋅ kg−1 ⋅ min−1) into 10 normal subjects. We found increasing doses of phenylephrine produced progressive increases in systolic blood pressure from 118 ± 4 to 129 ± 5 mmHg ( P < 0.005), R-R intervals from 881 ± 44 to 1,274 ± 69 ms ( P < 0.0001), and the logarithm of high-frequency power from 5.83 ± 0.22 to 7.73 ± 0.24 ln(ms2) ( P < 0.0001). The conclusion was high-frequency power increases with increasing doses of phenylephrine. These data strongly support the ability of high-frequency power to detect an increase in vagal modulation during baroreceptor activation from an increase in systolic blood pressure with the infusion of phenylephrine.
Mechanism of increased vessel wall nitric oxide concentrations during intestinal absorption
Authors: Bohlen H. Glenn
Published: December 2017

Vasoactive compounds, including nitric oxide (NO) and hypertonic sodium, may diffuse from venous endothelial cells and blood to the arterial wall during intestinal absorption. This hypothesis was tested by measuring the perivascular NO concentration ([NO]) for paired small arteries and veins with NO-sensitive microelectrodes. Resting arterial and venous wall concentrations for nine vessel pairs (5 rats) were 353 ± 28 and 401 ± 48 (SE) nM. During mucosal absorption of 100 and 300 mg/dl glucose, the artery dilated 12 ± 1.5 and 17 ± 2%, [NO] increased to 540 ± 68 and 550 ± 49 nM, and venous wall [NO] increased to 557 ± 60 and 633 ± 70 nM. During venous occlusion to block diffusion of materials from venous blood to the artery wall, the arterial and venous [NO] decreased by 70–80%, and one-half of the arterial dilation subsided. Superfusion with 320 and 360 mosmol/l hypertonic sodium medium to simulate the sodium hyperosmolarity during mucosal absorption of glucose increased the arterial [NO] by 20–30 and 40–50%; 360 mosmol/l saline made hypertonic with mannitol did not significantly increase the [NO]. Although venous to arterial diffusion of NO occurred, the increased arterial [NO] during mucosal glucose absorption was primarily generated by the arterial wall in response to materials that diffused from venous blood, such as hypertonic sodium.
Non-NMDA and NMDA receptors in the synaptic pathway between area postrema and nucleus tractus solitarius
Authors: Aylwin Maria Luz , Horowitz John M. , Bonham Ann C.
Published: December 2017

Area postrema (AP) modulates cardiovascular function through excitatory projections to neurons in nucleus tractus solitarius (NTS), which also process primary sensory (including cardiovascular-related) input via the solitary tract (TS). The neurotransmitter(s) and their receptors in the AP-NTS pathway have not been fully characterized. We used whole cell recordings in voltage- and current-clamp modes in the rat brain stem slice to examine the role of ionotropic glutamatergic receptors and α2-adrenergic receptors in the pathway from AP to NTS neurons receiving visceral afferent information via the TS. In neurons voltage clamped at potentials from −100 to +80 mV, AP stimulation (0.2 Hz) evoked excitatory postsynaptic currents having a fast component blocked by the non- N-methyl-d-aspartate (NMDA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulfonamide (NBQX; 3 μM, n = 7) and a slow component blocked by the NMDA receptor antagonistdl-2-amino-5-phosphonovaleric acid (APV; 50 μM, n = 8). Although NBQX (3 μM, n = 14) abolished AP-evoked action potentials, APV (50 μM, n = 9 or 500 μM, n = 6) or yohimbine, (200 nM, n = 5 or 2 μM, n = 10) did not. Thus, although AP stimulation activates both non-NMDA and NMDA receptors on NTS neurons receiving TS input, only non-NMDA receptors are required for synaptic transmission.
Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia
Authors: Cooper Anne , Heagerty Anthony M.
Published: December 2017

Vascular responses of human intramyocardial small arteries were examined in vitro to assess the influence of atherosclerosis and risk factors for coronary artery disease on endothelium-dependent relaxation. Recipient hearts were obtained from patients with ischemic ( n = 14) and nonischemic ( n = 13) cardiomyopathy undergoing heart transplantation. Small intramyocardial coronary arteries (mean internal diameter 313 ± 11 μm) were mounted on a wire myograph for measurement of morphology and isometric tension. Vasodilation was examined after preconstriction with U-46619, a thromboxane A2 analog. Endothelium-dependent relaxation to acetylcholine and bradykinin was impaired in patients with ischemic compared with nonischemic cardiomyopathy ( P < 0.01 and P < 0.001, respectively). Endothelium-independent relaxation to sodium nitroprusside was preserved. Incubation withl-arginine (3 mmol/l) did not improve endothelium-dependent relaxation to acetylcholine or bradykinin. With the use of stepwise multivariate analysis, hypercholesterolemia, but no other risk factor for atherosclerosis, was independently associated with impaired endothelium-dependent relaxation to acetylcholine ( r = −0.50, P = 0.05) but not to bradykinin. Endothelial dysfunction in intramyocardial small arteries may predispose patients with nonobstructive epicardial atherosclerosis and hypercholesterolemia to myocardial ischemia.
Seasonal Variation in Gastric Hydrochloric Acid Production in Rana Pipiens
Authors: Mizell Sherwin
Published: December 2017

Page 651: Sherwin Mizell, "Seasonal Variations in Gastric Hydrochloric Acid Production in Rana pipiens." In table 1, the headings of the 3rd, 4th, 8th and 9th columns should read microequivalents instead of milliequivalents.

Page 653: The ordinate in figure 1 b should read microequivalents/hour instead of milliequivalents/ hour.
Alveolar-Arterial Oxygen Tension Differences in Open-Chest Dogs
Authors: Williams M. H.
Published: December 2017

The alveolar-arterial oxygen tension difference has been measured in open-chest dogs both with the lung inflated and collapsed after expiration. In dogs with the lung inflated after expiration the tension differences varied with the magnitude of the alveolar ventilation and were similar to those seen in spontaneously breathing dogs and in intact dogs with positive-pressure respiration. Collapse of the lung resulted in an increase of the alveolar-arterial oxygen tension difference and appreciable tension differences were present during the inspiration of 12% and of 8% oxygen. The tension differences measured at three levels of oxygenation could be caused by the presence of different ventilation/perfusion ratios in various parts of the lung.
Some Characteristics of Hepatic Lymph in the Intact Rat
Authors: Friedman Meyer , Byers Sanford O. , Omoto Clarence
Published: December 2017

Detailed procedure for cannulation of the hepatic lymph duct and collection of hepatic lymph from rats is described. The average rate of flow of hepatic lymph from 12 rats so cannulated was 1.5 ml in 12 hours. The maximal pressure in four rats was sufficient to raise a column of lymph to a height of 26 cm. The albumin and globulin concentration of the hepatic lymph of six rats varied inversely with the volume collected and averaged two-thirds that of the serum, although qualitatively almost identical in electrophoretic studies. The glucose content of hepatic lymph was slightly higher than that of plasma (21 rats), while cholesterol content was less than that of plasma (28 rats). The urea and cholic acid concentrations were the same in plasma and hepatic lymph, within the limits of accuracy of the used (4 and 6 rats, respectively). Following biliary obstruction in six rats, the hepatic lymph contained increased amounts of cholic acid and bilirubin and was increased in volume to an average of 5.1 ml.
Pressure-Volume Curves of the Arterial and Venous Systems in Live Dogs
Authors: Guyton Arthur C. , Armstrong George G. , Chipley Patrick L.
Published: December 2017

Pressure-volume curves have been recorded for the arterial and the venous systems of live dogs. The quantity of blood in the arterial system of a 12-kg dog was found to average approximately 60 cc greater when the heart was pumping blood normally than when the circulation of blood was at a standstill. Likewise, under normal dynamic conditions the quantity of blood in the venous system of the 12-kg dog averaged 60 cc less than that under static conditions. The capacitance ( dV/dP) of the venous system, as calculated from the pressure-volume curves, averaged between 18 and 30 times as great as the capacitance of the arterial system. This means that for each unit change in blood pressure the venous system can hold 18–30 times as much blood as can the arterial system within the range of pressures measured in this study.
Role of Histamine and Leucotaxin in Function of Cellular Defense Mechanism
Authors: Kátó László , Gözsy Béla
Published: December 2017

Experiments are presented to the effect that in an inflammatory process histamine and leucotaxin appear successively at different and orderly time intervals, thus assuring an increased fluid flow through the capillary wall. Histamine is released not only in the inflammatory process but also by intradermal administration of such substances (volatile oils or their components) which induce neither the triple response of Th. Lewis nor any tissue damage. This could be explained by the fact that in the tissues histamine is ‘present’ but leucotaxin is ‘formed.’
Metabolism of Lactic Acid in the Intact Rabbit
Authors: Drury Douglas R. , Wick Arne N.
Published: December 2017

The metabolism of the lactic acid was studied in normal intact rabbits making use of C14 labeled l (+) lactate. The circulating lactate is being used up and renewed at a rapid rate. The turnover time is about 30 minutes. Eighty to ninety per cent of the lactate is disposed of by direct oxidation. Only a small percentage can be accounted for as glucose, glycogen and by the oxidation of these. Lactate that is produced in emergency states can serve as a quick fuel for vital tissues in these situations.
Adrenocortical Activity and Metabolism of 17-Hydroxycorticosteroids in Thyroidectomized Dogs
Authors: Eik-Nes Kristen , Brizzee Kenneth R.
Published: December 2017

Low or zero levels of plasma 17-hydroxycorticosteroids and a reduced adrenocortical capacity were found in dogs at the 7th day following thyroidectomy. The daily administration of l-thyroxine to thyroidectomized dogs restored normal adrenocortical function. Low but measurable levels of plasma 17-hydroxycorticosteroids were present in dogs 30 days after thyroidectomy, whereas an apparent normal removal rate of intravenously given cortisol (compound F), was present both at the 7th and at the 30th day after thyroidectomy. Since sham operations or other ‘stress’ forms were not associated with reduced adrenocortical function either on the 7th or on the 30th day post ‘stress,’ a thyroid-adrenal metabolic interaction is postulated.
Water Absorption From the Intestine via Portal and Lymphatic Pathways
Authors: Benson John A. , Lee Philip R. , Scholer John F. , Kim Kwang S. , Bollman Jesse L.
Published: December 2017

The content of either D2O or Na24 has been measured in the intestinal lymph, portal venous blood, and femoral arterial blood of unanesthetized hydrated rats after administration of the isotope into the stomach, duodenum, or peripheral or portal vein. Little, if any, water or sodium ion is delivered to the body by a lymphatic pathway after absorption from the small intestine. At least 99% is carried in portal venous blood. The amount of isotope found in intestinal lymph was proportional to lymph volume whatever the route of administration, and derived mainly from the arterial blood. Even during absorption of water or sodium ion from the small intestine the arterial circulation is the principal source of the water and sodium of the lymph.
Water and Electrolyte Balance of Goldfish Under Conditions of Anoxia, Cold and Inanition
Authors: Meyer D. K. , Westfall B. A. , Platner W. S.
Published: December 2017

Small goldfish ( Carassius auratus), average length 38 mm, were exposed to three conditions of stress, namely, acute anoxia, cold and inanition. Acute anoxia did not alter Na or K content of the body, but water increased 0.85%. Exposure to 4.0°C for 48 hours increased the water content 2.15%, but no change occurred in the absolute values of Na and K. Inanition for 2 and 7 weeks caused a progressive loss in dry weight without significantly altering the absolute amount of water. However, when total water was calculated on a dry weight basis, the increase was 3.81% for 2 weeks fasting and 6.74% for 7 weeks fasting. Sodium increased in absolute amount with fasting while K decreased. This inverse relationship showed a high correlation. For every milliequivalent of K lost, 1.2 mEq of Na was taken up. An important difference between the period of 2 and 7 weeks of fasting is discussed with respect to Na and K and their role in carbohydrate, fat and protein depletion.
Leucocyte Changes in Rodents Exposed to Cold With and Without Restraint
Authors: Lavenda Nathan , Bartlett Roscoe G. , Kennedy Vira E.
Published: December 2017

The white blood cell picture was determined in adult mice and rats with and without restraint. In the mouse both cold and restraint resulted in lymphopenia. When the stresses were applied simultaneously the effect was additive. Restraint in the mouse also caused a reduction in the polymorphonuclear elements. In the rat, restraint produced lymphopenia but contrary to the mouse the stress response of the polymorphonuclear leucocytes was a slight increase rather than a decrease. The total heart white blood cell count was much lower in the mouse than in the rat. Cold was the more severe stress for the mouse, whereas only restraint appeared to be effective in the rat. The possible mechanisms responsible for these treatment and species differences are discussed.
Effect of Bilateral Nephrectomy on Peripheral Vascular Reactivity of Dogs
Authors: Vanatta John C. , Danhof Ivan , McMullen Mimi
Published: December 2017

The reactivity of 20 dogs to 0.5 µ/kg of norepinephrine was determined. Eleven dogs were bilaterally nephrectomized ( I), six underwent bilateral sham nephrectomy ( II), and 3 underwent unilateral sham operations followed by contralateral nephrectomy ( III). The results of II and III were pooled for statistical purposes. The average change in reactivity in I was significantly higher than the average change in reactivity in II and III on both the 1st and the 2nd postoperative days. There was no significant difference in blood pressure observed between the two series before the operations.
Ketone Body Metabolism in Ascorbic Acid Deficiency
Authors: Debons Albert F. , Wallace John W. , Bacchus Habeeb
Published: December 2017

The in vitro formation of ketone bodies by liver tissues of ascorbic acid-deficient, and control (pair-fed) guinea pigs was studied. The data revealed that the spontaneous production of ketone bodies by the liver of the ascorbic acid-deficient guinea pig is less than that of the control animal. The capacity of the liver of the deficient guinea pig to form ketone bodies from octanoate exceeds that of control animals. The total fat content and the liver weight are not significantly altered in ascorbic acid-deficiency. The data suggest that the diminished spontaneous production of ketone bodies by the ascorbic acid-deficient liver, in spite of its normal content of fat, might be secondary to a diminished fatty acid formation from endogenous fat. In the presence of fatty acid substrate the formation of ketone bodies by the ascorbic acid-deficient liver is not appreciably disturbed.
Relation of Tissue Extensibility to Smooth Muscle Tone
Authors: Remington J. W. , Alexander R. S.
Published: December 2017

Isolated specimens of rabbit gut or bladder were subjected to fixed loads, length changes being recorded kymographically. The elongation curves showed two essential phases. First there was a rapid visco-elastic extension whose amount was directly related to load. Second, there was a sustained creep whose slope was less clearly dependent upon load. This creep appeared not to develop until a critical load value was exceeded. A stretch reduced the viscosity, as reflected in the initial extension of a succeeding stretch. This change could be reversed with long recovery intervals allowed after load removal. Load removal was followed by a brief viscoelastic recoil, and then a long term length retraction which had the same slope regardless of the amount of prior extension. The recoil was always less in amount than the previous visco-elastic extension. The recovery of the initial viscosity, with time, could not be related to the recovery in length. While acetylcholine or epinephrine could change the tissue length, they had no clear effect upon the amount or rate of initial extension, upon the late creep, or upon the late length retraction upon load release. The contractile elements of the muscle would seem to be in series with visco-elastic elements, and the elongation pattern of the latter dominantly controls the over-all tissue extensibility. Only in a few cases can the tissue extensibility be related to the amount of muscle contraction.
Composition and Osmolarity of Gastric Juice as a Function of Plasma Osmolarity
Authors: Thull Nicholas B. , Rehm Warren S.
Published: December 2017

The composition of gastric juice during the initial phases of secretion in stomachs washed with distilled water is different than in unwashed stomachs. Stomachs not secreting acid were washed with distilled water and it was found that considerably more Na+ ion than K+ ion entered the water. Intravenous hypertonic loading with 0.64 m NaCl results in a) a decrease in the volume of secretion, b) a tendency for the osmolarity of gastric juice to increase in the early phases of loading and a decline to a level lower than the normal level in the later phases of loading, c) a decrease in the ratio of the osmolarity of gastric juice to that of plasma which is associated with a simultaneous increase in the Na+ ion concentration and a decrease in H+ ion concentration of gastric juice, and d) relatively little change in the K+ ion concentration. Intravenous injections of 0.04 m NaCl results in a) an increase in the volume of secretion during the early phases, b) a decrease in osmolarity of the gastric juice and c) relatively little change in the Na+ and K+ ion concentrations. These data are analyzed on the basis of a previously proposed hypophysis.
Measurement of Splanchnic Blood Volume in Dogs
Authors: Johnstone F. R. C.
Published: December 2017

The splanchnic blood volume of dogs has been measured, the method employing P32-labeled red cells, and requiring evisceration of the animal. In 10 dogs this amounted on the average to 21.7% of the circulating blood volume, or 17.7 ml/kg body weight.
Effect of Temperature on Sodium Reabsorption in the Perfused Bullfrog Kidney
Authors: Hoshiko T.
Published: December 2017

The bullfrog kidney was perfused with a PVP-Conway fluid at constant temperatures ranging from 6–27°C. At the higher temperatures the urine sodium concentration was initially low and rose rapidly, while at the lower temperatures, the urinary sodium started high and rose less steeply. The logarithm of the calculated net sodium reabsorption rate fell linearly with time, independently of changes in filtered load. At the higher temperatures the initial sodium reabsorption rate was higher but fell more rapidly than at the lower temperatures. The initial values for sodium reabsorption were used to calculate the Arrhenius activation energy, which was found to be approximately 29 Cal/m. The exponential fall in sodium reabsorption was interpreted in terms of a carrier diffusion limited system as the mechanism of active transport.
Relationship Between Growth and Muscle Creatine Levels in Young Rats Fed Supplementary Folacin, B12 and Methylating Agents With and Without Glycocyamine
Authors: Poutsiaka John W.
Published: December 2017

A simple and reliable method of extracting creatine from muscle for analysis as creatinine is described. In the absence of exogenous glycocyamine, growth was accelerated but muscle creatine levels were reduced in rats fed folacin and B12, either alone, or with methionine; growth was also accelerated in rats given folacin and B12 with choline, however, muscle creatine levels in these animals were increased rather than reduced. In the presence of exogenous glycocyamine, growth was depressed but muscle creatine was enhanced or maintained at a high level, respectively, in rats fed folacin and B12, or folacin and B12 with choline; muscle creatine levels were increased without significant growth depression in rats given glycocyamine with folacin, B12 and methionine.
Interaction of Vestibular and Proprioceptive Reflexes in the Decerebrate Cat
Authors: Koella Werner P. , Nakao Hiroyuki , Evans Robert L. , Wada Jun
Published: December 2017

The quantitative interrelation between stretch, tension and position in space was studied in decerebrate cats. The tension produced by the isolated M. triceps brachii was recorded by means of strain gauges. It was found that the tension increment, produced by a particular stretch, increases as the preparation is turned from the prone to the supine position around its longitudinal axis. The proportion between the tensions produced by a series of two or more different stretches, however, stays constant under these conditions. It was shown, furthermore, that the effect of a change in position upon the degree of rigidity—i.e., the difference between the tensions in the prone and in the supine positions—is the greater the greater the initial stretch. A quantitative analysis of the results disclosed that the vestibular factor and the proprioceptive factor are related in a multiplicative manner. These experiments show that the vestibular apparatus and the muscle spindles exert their influence not in an isolated and independent, but a quantitatively interdependent manner. The results of the present work together with the findings of other authors (Granit) give strength to the argument that the vestibular apparatus controls the stretch reflex activity in an indirect manner, i.e., over the ‘by-pass’ of the gamma-efferents.
Experimental Motion Sickness in Dogs
Authors: Wang S. C. , Chinn Herman I.
Published: December 2017

Motion sickness was experimentally induced in dogs by means of a standardized swinging exposure. Susceptible dogs were selected for surgical extirpation of the labyrinths or various parts of the cerebellum. It was found that animals showed no vomiting responses to long exposures of swinging motion after bilateral labyrinthectomy or ablation of the nodulus and uvula. Even with incomplete extirpation of these structures, animals would become partially or totally resistant to motion sickness. In general, these operated animals exhibited normal responses to intravenously administered apomorphine or orally administered copper sulfate. These results indicate that motion stimulates the labyrinthine receptors, and the vestibular impulses traverse the nodulus and uvula of the cerebellum, and the chemoceptive emetic trigger zone, and finally reach the medullary vomiting center.
Mechanism of Early and Chronic Experimental Renal Hypertension as Tested by CCK-179
Authors: Oyen Irene H.
Published: December 2017

The effects on blood pressure and renal clearances of a combination of dihydrogenated ergot alkaloids, CCK-179, were studied in normal dogs and dogs with experimental renal (Goldblatt) hypertension. The drug was observed to have a maximal effect at 0.012 mg/kg, about one twelfth to one sixteenth the dose recommended in the literature. In normal dogs the drug causes a slight fall in blood pressure, a moderate decrease in glomerular filtration rate (creatinine clearance) and a pronounced decrease in renal plasma flow (PAH clearance), hemodynamic effects resembling those seen in man. After repeated administration of the drug, the renal effects are of greater magnitude in these dogs. In hypertensive dogs, CCK-179 causes blood pressure to approach normal levels. In the early weeks of hypertension, the renal effects of the drug are similar to those seen in normals but as hypertension increases in duration up to 55 weeks, the decreases in filtration rate and plasma flow become progressively smaller. This could indicate that in chronic experimental renal hypertension the high peripheral resistance is maintained at least in part by increased activity of the sympathetic nervous system rather than by the action of the components of the renal humoral pressor system.