bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of long-term experimental orthostatic body position on innervation density in extremity vessels
Authors: Monos E. , Lóránt M. , Fehér E.
Published: December 2017

The aim of this study was to quantitate the density of nerve terminals as well as their synaptic vesicle population in the adventitia of saphenous (SV and SA) and brachial veins and arteries (BV and BA) obtained from rats maintained in a horizontal control or a tilted position. Adult animals were kept individually in tubelike cages in a 45° head-up position. After 2 wk, both tilted and control animals were anesthetized, and the whole body was perfused with fixative solution at physiological pressure. Vessels segments were then excised for electron microscopy and immunohistochemistry. The nerve terminal density (NTD) of SA was 8.20 ± 1.46 nerve terminals/100 μm2cross section of adventitia and that of SV was 4.53 ± 0.61 nerve terminals/100 μm2cross section of adventitia in control rats. Tilting caused a significant increase in NTD of both SA (70%) and SV (52%). The synaptic microvesicle density (SyVD) was larger in SA than SV in control rats (30.48 ± 4.41 vs. 13.38 ± 2.61 synaptic vesicles/10 terminal sections), but tilting resulted in more pronounced changes in SyVD of SV (95%) than SA (54%). No significant changes in NTD and SyVD of BA were found after tilt (−3.6% relative to 4.99 ± 0.33 compared with 0.4% relative to 24.89 ± 3.7, respectively). Whereas NTD of BV exhibited a tendency to increase (3.73 ± 0.86 vs. 2.31 ± 0.29 nerve terminals/100 μm2cross section of adventitia), SyVD did not change significantly (18.96 ± 2.74 vs. 22.85 ± 3.17 synaptic vesicles/10 terminal sections). A large number of nerve terminals of all vessels were tyrosine hydroxylase immunoreactive (containing norepinephrine). These findings support the hypothesis that long-term gravitational load causes adaptive morphological and functional remodeling of sympathetic innervation in blood vessels of the extremities.
Bradykinin receptor antagonists attenuate neointimal proliferation postangioplasty
Authors: Yau Lorraine , Wilson David P. , Werner Jeffery P. , Zahradka Peter
Published: December 2017

Bradykinin has been linked to the development of restenosis in response to vascular injury. We therefore examined the effect of bradykinin on vascular smooth muscle cell growth and neointimal formation in organ culture. Bradykinin stimulated both RNA and DNA synthesis (by 175%) in smooth muscle cells from either porcine or human coronary arteries and increased cell number in a concentration-dependent manner. Both p42/44 mitogen-activated protein kinase (MAPK) and p38 kinase were also activated. Treatment with [Hyp3,Tyr(Me)8]bradykinin, a B2receptor agonist, stimulated thymidine incorporation by 146%, whereas B1-selective Lys-des-Arg9-bradykinin had no effect. Addition of the B2antagonist HOE-140 reduced the stimulation by 56%, whereas B1-selective des-Arg-HOE-140 had no significant effect. Similarly, HOE-140 attenuated angioplasty-induced neointimal formation in organ culture with an efficacy approaching 100% inhibition. These experiments suggest that bradykinin promotes smooth muscle proliferation after vascular injury, presumably via B2receptor-dependent activation of MAPK family pathways, and may explain the negative outcome of angiotensin converting enzyme inhibitor therapy on restenosis in nonrodent models.
Effects of pituitary adenylate cyclase-activating polypeptide on canine atrial electrophysiology
Authors: Hirose Masamichi , Leatmanoratn Zeng , Laurita Kenneth R. , Carlson Mark D.
Published: December 2017

We hypothesized that pituitary adenylate cyclase-activating polypeptide (PACAP) activates intracardiac postganglionic parasympathetic nerves and has a different effect than cervical vagal stimulation. We measured effective refractory period (ERP) and conduction velocity at four atrial sites [high right atrium (HRA), low right atrium (LRA), high left atrium (HLA), and low left atrium (LLA)] and minimum atrial fibrillation (AF) cycle length at 12 atrial sites during cervical vagal stimulation and after PACAP in 26 autonomically decentralized, open-chest, anesthetized dogs. PACAP shortened ERP to a similar extent at all four sites (HRA, 58 ± 2.0 ms; LRA, 60 ± 6.3 ms; HLA, 68 ± 11.5 ms; and LLA, 60 ± 8.3 ms). Low- and high-intensity vagal stimulation shortened ERP at the HRA, but not in the other atrial sites (low-intensity stimulation: HRA, 64 ± 4.0 ms; LRA, 126 ± 5.1 ms; HLA, 110 ± 9.5 ms; and LLA, 102 ± 11.5 ms; high-intensity stimulation: HRA, 58 ± 4.2 ms; and HLA, 101 ± 4.0 ms). Conduction velocity was not altered by any intervention. Minimum AF cycle length after PACAP was similar in both atria but was shorter in the right atrium than in the left atrium during vagal stimulation. After atropine administration, no interventions changed ERP. These results suggest that PACAP shortens atrial refractoriness uniformly in both atria through activation of intrinsic cardiac nerves, not all of which are activated by cervical vagal stimulation.
Signal-transducing function of Na+-K+-ATPase is essential for ouabain's effect on [Ca2+]iin rat cardiac myocytes
Authors: Tian Jiang , Gong Xiaohua , Xie Zijian
Published: December 2017

We showed before that Na+-K+-ATPase is also a signal transducer in neonatal rat cardiac myocytes. Binding of ouabain to the enzyme activates multiple signal pathways that regulate cell growth. The aims of this work were to extend such studies to adult cardiac myocytes and to determine whether the signal-transducing function of Na+/K+-ATPase regulates the well-known effects of ouabain on intracellular Ca2+concentration ([Ca2+]i). In adult myocytes, ouabain activated protein tyrosine phosphorylation and p42/44 mitogen-activated protein kinases (MAPKs), increased production of reactive oxygen species (ROS), and raised both systolic and diastolic [Ca2+]i. Pretreatment of myocytes with several Src kinase inhibitors, or overexpression of a dominant negative Ras, antagonized ouabain-induced activation of MAPKs and increases in [Ca2+]i. Treatment with PD-98059 (a MAPK kinase inhibitor) or overexpression of a dominant negative MAPK kinase 1 also ablated the effect of ouabain on MAPKs and [Ca2+]i. N-acetyl-cysteine, which blocks the effect of ouabain on ROS, did not prevent the ouabain-induced rise in [Ca2+]i. Clearly, the activation of the Ras/MAPK cascade, but not ROS generation, is necessary for ouabain-induced increases in [Ca2+]iin rat cardiac myocytes.
Chronic decentralization of the heart differentially remodels canine intrinsic cardiac neuron muscarinic receptors
Authors: Smith F. M. , McGuirt A. S. , Hoover D. B. , Armour J. A. , Ardell J. L.
Published: December 2017

The objective of the study was to determine if chronic interruption of all extrinsic nerve inputs to the heart alters cholinergic-mediated responses within the intrinsic cardiac nervous system (ICN). Extracardiac nerve inputs to the ICN were surgically interrupted (ICN decentralized). Three weeks later, the intrinsic cardiac right atrial ganglionated plexus (RAGP) was removed and intrinsic cardiac neuronal responses were evaluated electrophysiologically. Cholinergic receptor abundance was evaluated using autoradiography. In sham controls and chronic decentralized ICN ganglia, neuronal postsynaptic responses were mediated by acetylcholine, acting at nicotinic and muscarinic receptors. Muscarine- but not nicotine-mediated synaptic responses that were enhanced after chronic ICN decentralization. After chronic decentralization, muscarine facilitation of orthodromic neuronal activation increased. Receptor autoradiography demonstrated that nicotinic and muscarinic receptor density associated with the RAGP was unaffected by decentralization and that muscarinic receptors were tenfold more abundant than nicotinic receptors in the right atrial ganglia in each group. After chronic decentralization of the ICN, intrinsic cardiac neurons remain viable and responsive to cholinergic synaptic inputs. Enhanced muscarinic responsiveness of intrinsic cardiac neurons occurs without changes in receptor abundance.
Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice
Authors: Hart Chari Y. T. , Burnett John C. , Redfield Margaret M.
Published: December 2017

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (τ), and the first derivatives of LV pressure rise and fall (dP/d t max and dP/d t min, respectively). During echocardiography, HR was lower in XK than AV mice (250 ± 14 beats/min in XK vs. 453 ± 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 ± 0.08 mm in XK vs. 3.8 ± 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 ± 1.2% in XK vs. 40 ± 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 ± 24 beats/min) and XK (342 ± 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 ± 5 vs. 6.2 ± 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/d t max: 4,402 ± 798 vs. 8,250 ± 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (τ: 23 ± 2 vs. 14 ± 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.
Increased [Mg2+]oreduces Ca2+ influx and disruption of mitochondrial membrane potential during reoxygenation
Authors: Sharikabad Mohammad Nouri , Østbye Kirsten Margrethe , Brørs Odd
Published: December 2017

Increase in extracellular Mg2+concentration ([Mg2+]o) reduces Ca2+ accumulation during reoxygenation of hypoxic cardiomyocytes and exerts protective effects. The aims of the present study were to investigate the effect of increased [Mg2+]o on Ca2+ influx and efflux, free cytosolic Ca2+([Ca2+]i) and Mg2+ concentrations ([Mg2+]i), Ca2+ accumulation in the presence of inhibitors of mitochondrial or sarcoplasmatic reticulum Ca2+ transport, and finally mitochondrial membrane potential (Δψm). Isolated adult rat cardiomyocytes were exposed to 1 h of hypoxia and subsequent reoxygenation. Cell Ca2+ was determined by 45Ca2+uptake, and the levels of [Mg2+]i and [Ca2+]i were determined by flow cytometry as the fluorescence of magnesium green and fluo 3, respectively. Ca2+ influx rate was significantly reduced by ∼40%, whereas Ca2+ efflux was not affected by increased [Mg2+]o (5 mM) during reoxygenation. [Ca2+]i and [Mg2+]iwere increased at the end of hypoxia, fell after reoxygenation, and were unaffected by increased [Mg2+]o. Clonazepam, a selective mitochondrial Na+/Ca2+exchange inhibitor (100 μM), significantly reduced Ca2+accumulation by 70% and in combination with increased [Mg2+]o by 90%. Increased [Mg2+]o, clonazepam, and the combination of both attenuated the hypoxia-reoxygenation-induced reduction in Δψm, determined with the cationic dye JC-1 by flow cytometry. A significant inverse correlation was observed between Δψm and cell Ca2+ in reoxygenated cells treated with increased [Mg2+]o and clonazepam. In conclusion, increased [Mg2+]o(5 mM) inhibits Ca2+ accumulation by reducing Ca2+ influx and preserves Δψm without affecting [Ca2+]i and [Mg2+]i during reoxygenation. Preservation of mitochondria may be an important effect whereby increased [Mg2+]o protects the postischemic heart.
Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation
Authors: Borutaite Vilmante , Matthias Anita , Harris Hatty , Moncada Salvador , Brown Guy C.
Published: December 2017

Incubation of rat aortas with endotoxin and interferon-γ for 24 h resulted in an aortic oxygen consumption that was substantially inhibited and strongly oxygen dependent (37% inhibition at 160 μM O2 and 62% inhibition at 80 μM O2 relative to untreated aortas). This respiratory inhibition was reversed by a nitric oxide (NO) scavenger (oxyhemoglobin) or by an inhibitor of inducible NO synthase [ N-(3-(aminomethyl)benzyl)acetamide · 2HCl, 1400W], but not by an inhibitor of soluble guanylate cyclase (1 H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one). Addition of 1 μM NO to untreated aortas caused rapid and reversible inhibition of oxygen consumption that was greater at lower oxygen concentrations. Incubation of endothelial cells isolated from rat aortas with endotoxin and interferon-γ for 24 h resulted in a steady-state NO concentration of ∼0.5 μM and 90% inhibition of cellular oxygen consumption that was immediately reversed by an NO scavenger (oxyhemoglobin). These results suggest that during inflammation and sepsis, tissue respiration may be substantially reduced due to inhibition by NO of cytochrome oxidase.
Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO
Authors: Nikolaidis Lazaros A. , Hentosz Teresa , Doverspike Aaron , Huerbin Rhonda , Stolarski Carol , Shen You-Tang , Shannon Richard P.
Published: December 2017

Incessant tachycardia induces dilated cardiomyopathy in humans and experimental models; mechanisms are incompletely understood. We hypothesized that excessive chronotropic demands require compensatory contractility reductions to balance metabolic requirements. We studied 24 conscious dogs during rapid right ventricular (RV) pacing over 4 wk. We measured hemodynamic, coronary blood flow (CBF), myocardial O2 consumption (MV˙o 2) responses, myocardial nitric oxide (NO) production, and substrate utilization. Early pacing (6 h) resulted in decreased heart rate (HR)-adjusted coronary blood flow (CBF), MV˙o 2 (CBF/beat: 0.33 ± 0.02 to 0.19 ± 0.01 ml, P < 0.001, MV˙o 2/beat: 0.031 ± 0.002 to 0.016 ± 0.001 ml O2, P < 0.001), and contractility [left ventricular (LV) first derivative pressure (dP/d t)/LV end-diastolic diameter (EDD): 65 ± 4 to 44 ± 3 mmHg · s−1 · mm−1, P < 0.01], consistent with flow-metabolism-function coupling, which persisted over the first 72 h of pacing (CBF/beat: 0.15 ± 0.01 ml, MV˙o 2/beat: 0.013 ± 0.001 ml O2, P < 0.001). Thereafter, CBF per beat and MV˙o 2 per beat increased (CBF/beat: 0.25 ± 0.01 ml, MV˙o 2/beat: 0.021 ± 0.001 ml O2 at 28 days, P < 0.01 vs. 72 h). Contractility declined [(LV dP/d t)/LVEDD: 19 ± 2 mmHg · s−1 · mm−1, P < 0.0001], signifying flow-function mismatch. Cardiac NO production, endothelial NO synthase expression, and fatty acid utilization decreased in late phase, whereas glycogen content and lactate uptake increased. Incessant tachycardia induces contractile, metabolic, and flow abnormalities reflecting flow-function matching early, but progresses to LV dysfunction late, despite restoration of flow and metabolism. The shift to flow-function mismatch is associated with impaired myocardial NO production.
Nitric oxide and cGMP protein kinase activity in aged ventricular myocytes
Authors: Zhang Qihang , Molino Bruno , Yan Lin , Haim Todd , Vaks Yakir , Scholz Peter M. , Weiss Harvey R.
Published: December 2017

We tested the hypothesis that nitric oxide-induced negative functional effects through cGMP would be reduced in aged cardiac myocytes. Maximum rate of shortening ( Rmax) and percent shortening of ventricular myocytes from young (6 mo) and old (3 y) rabbits were studied using a video edge detector. cGMP-dependent phosphorylation was examined by electrophoresis and autoradiography. Myocytes received a nitric oxide donor S-nitroso- N-acetyl-penicillamine (SNAP, 10−7, 10−6, and 10−5M) followed by KT-5823 (10−6M), a cGMP protein kinase inhibitor. Baseline function was similar in young and old myocytes (89.1 ± 4.5 young vs. 86.4 ± 8.3 μm/s old Rmax, 5.6 ± 0.3 vs. 5.2 ± 0.7%shortening). SNAP (10−5M) decreased Rmaxin both young (25%, n = 6) and old myocytes (24%, n = 7). SNAP also reduced percent shortening by 28% in young and 23% in old myocytes. The negative effects of SNAP were partially reversed by KT-5823 only in young myocytes. Multiple proteins were phosphorylated by cGMP, and KT-5823 could reduce this effect. The degree of phosphorylation was significantly less in old myocytes. These results suggest that the functional response of ventricular myocytes to nitric oxide was preserved during aging. However, the importance of cGMP-dependent protein phosphorylation was decreased, indicating a shift to other pathways.
Mechanism of α-adrenergic regulation of expressed hKv4.3 currents
Authors: Po Sunny S. , Wu Richard C. , Juang George J. , Kong Wei , Tomaselli Gordon F.
Published: December 2017

The transient outward potassium current ( I to) is an important repolarizing current in the mammalian heart. I to is regulated by adrenergic stimulation; however, the effect of agonists on this current, and consequently the action potential duration and profile, is variable. An important source of the variability is the difference in the channel genes that underlie I to. There are two subfamilies of candidate genes that are likely to encode I to in the mammalian heart: Kv4 and Kv1.4; the predominance of either gene is a function of the species, stage of development, and region of the heart. The existence of different isoforms of the Kv4 family (principally Kv4.2 or Kv4.3) further complicates the effect of α-adrenergic modulation of cardiac I to. In the human ventricle, hKv4.3 is the predominant gene underlying I to. Two splice variants of human Kv4.3 (hKv4.3) are present in the human ventricle; the longer splice variant contains a 19-amino acid insert in the COOH-terminus with a consensus protein kinase C (PKC) site. We used heterologous expression of hKv4.3 splice variants and studies of human ventricular myocytes to demonstrate that α-adrenergic modulation of I to occurs through a PKC signaling pathway and that only the long splice variant (hKv4.3-L) is modulated via this pathway. Only a single hKv4.3-L monomer in the tetrameric I to channel is required to confer sensitivity to phenylephrine (PE). Mutation of the PKC site in hKv4.3-L eliminates α-adrenergic modulation of the hKv4.3-encoded current. The similar, albeit less robust, modulation of human ventricular I to by PE suggests that hKv4.3-L is expressed in a functional form in the human heart.
Membrane depolarization, elevated Ca2+entry, and gene expression in cerebral arteries of hypertensive rats
Authors: Wellman G. C. , Cartin L. , Eckman D. M. , Stevenson A. S. , Saundry C. M. , Lederer W. J. , Nelson M. T.
Published: December 2017

Elevated intracellular Ca2+([Ca2+]i) has been implicated in contractile and phenotypic changes in arterial smooth muscle during hypertension. This study examined the role of membrane potential and [Ca2+]iin altered gene expression in cerebral arteries of a rat (Dahl) genetic model of salt-sensitive hypertension. Cerebral arteries from hypertensive animals (Dahl salt-sensitive) exhibited a tonic membrane depolarization of ∼15 mV compared with normotensive (Dahl salt-resistant) animals. Consistent with this membrane depolarization, voltage-dependent K+currents were decreased in cerebral artery myocytes isolated from hypertensive animals. Arterial wall Ca2+was elevated in cerebral arteries from hypertensive animals, an effect reversed by diltiazem, a blocker of voltage-dependent Ca2+channels. This depolarization-induced increase in [Ca2+]iwas associated with increased activation of the transcription factor, cAMP response element binding protein, and increased expression of the immediate early gene c-fos, both of which are reversed by acute exposure to the voltage-dependent Ca2+channel blocker nisoldipine. This study provides the first information linking altered Ca2+handling to changes in gene expression in cerebral arteries during hypertension.
Oxygen diffusion and consumption of aortic valve cusps
Authors: Weind K. L. , Boughner D. R. , Rigutto L. , Ellis C. G.
Published: December 2017

To maintain tissue oxygenation, normal aortic valves contain a vascular bed where tissue thickness is greatest. Avascular “living” tissue-engineered heart valves have been proposed, yet little information exists regarding the magnitude of valve tissue metabolic activity or oxygen requirements. We therefore set out to measure the oxygen diffusivity (Do2 ) and oxygen consumption (V˙o 2) of seven porcine aortic valve cusps in vitro at 37°C using a chamber with a Clark oxygen sensor. MeanDo2 and V˙o 2 were 1.06 × 10−5 cm2/s and 3.05 × 10−5 · ml O2 · ml tissue−1 · s−1, respectively. When modeled as a three-layered structure by using these values and a boundary condition of 100 mmHg at both surfaces, the average aortic cusp predicted a central mean Po 2 of 27 mmHg (range of 0–50 mmHg). The Do2 value obtained was similar to that found for other vascular structures, but because our studies were carried out in vitro, theV˙o 2 measurements may be lower than that required by the functioning valves. These values provide an initial understanding of the oxygen supply possible from the cusp surfaces and the oxygen needs of the tissue.
Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure
Authors: Nakamura Ryo , Egashira Kensuke , Arimura Kenichi , Machida Youji , Ide Tomomi , Tsutsui Hiroyuki , Shimokawa Hiroaki , Takeshita Akira
Published: December 2017

Recent evidence suggests that increased inactivation of endothelium-derived nitric oxide (NO) by oxygen free radical (OFR) formation is involved in the pathogenesis of endothelial dysfunction in heart failure (HF). However, it is unclear whether increased OFR limits coronary flow reserve in HF. To test this hypothesis, we examined the effects of antioxidant therapy on coronary flow reserve in a canine model of tachycardia-induced HF. The flow reserve (percent increase in coronary blood flow) to adenosine or to 20-s ischemia was less and OFR formation (electron-spin resonance spectroscopy) in myocardial tissues was greater in HF dogs than in controls. Immunohistochemical staining of 4-hydroxy-2-nonenal, an OFR-induced lipid peroxide, was detected in coronary microvessels of HF dogs. Intracoronary infusion of a cell-permeable OFR scavenger, tiron, suppressed OFR formation and improved the vasodilating capacity to adenosine or brief ischemia in HF dogs but not in controls. A NO synthesis inhibitor, N G-monomethyl-l-arginine (l-NMMA), diminished the beneficial effects of tiron in HF dogs. Vasodilation to sodium nitroprusside was similar between control and HF dogs, and no change in its response was noted with tiron or tiron + l-NMMA in either group. In summary, antioxidant treatment with tiron improved coronary flow reserve by increasing NO bioactivity in HF dogs. Thus increased OFR formation may impair coronary flow reserve in HF by reducing NO bioactivity.
Differential effects of histamine and thrombin on endothelial barrier function through actin-myosin tension
Authors: Moy Alan B. , Blackwell Ken , Kamath Anant
Published: December 2017

We compared temporal changes in isometric tension in cultured human umbilical vein endothelial cells inoculated on a polymerized collagen membrane with changes in cell-cell and cell-matrix adhesion derived by a mathematical model of transendothelial cell resistance. Thrombin and histamine disrupt barrier function by targeting a greater loss in cell-cell adhesion, which preceded losses in overall transendothelial resistance. There were minor losses in cell-matrix adhesion, which was temporally slower than the decline in the overall transendothelial resistance. In contrast, thrombin and histamine restored barrier function by initiating a restoration of cell-matrix adhesion, which occurred before an increase in overall transendothelial resistance. Thrombin mediated a second and slower decline in cell-cell adhesion, which was not observed in histamine-treated cells. This decline in cell-cell adhesion temporally correlated with expressed maximal levels of tension development, suggesting that actin-myosin contraction directly strains cell-cell adhesion sites. Pretreatment of cells with ML-7 mediated more rapid recovery of cell-cell adhesion and had no effect on cell-matrix adhesion. Taken together, expression of actin-myosin contraction affects the restoration of barrier function by straining cell-cell adhesion sites.
Effects of age, gender, and blood pressure on myogenic responses of mesenteric arteries from C57BL/6 mice
Authors: Gros Robert , Van Wert Ryan , You Xiaomang , Thorin Eric , Husain Mansoor
Published: December 2017

The myogenic response (MR) may represent an important physiological parameter underlying arterial blood pressure (BP). We studied the effects of age, gender, and BP on the MR of mesenteric arteries from 8- to 52-wk-old mice. Increasing age and BP are associated with an increase in the perfusion pressure at which tone develops (myogenic set point). An inverse correlation exists between age and extent (magnitude) of the MR in male ( r 2 = 0.93, P = 0.0087) and female mice ( r 2 = 0.90, P = 0.013) as well as between BP and extent of the MR in male ( r 2 = 0.96, P = 0.0036) and female ( r 2 = 0.90, P = 0.014) mice. In contrast, the strength of the MR (slope of active diameter-pressure relationship) and phenylephrine-mediated constriction did not differ among these groups. Although gender had no effect on MR at any perfusion pressure or age, only male mice showed significant salt-induced hypertension and an associated increase in the set point and reduction in the extent of the MR. The set point and extent of the MR is linked to the in vivo pressure during development and experimental hypertension.
Role of active transport of chloride in formation of dogfish cerebrospinal fluid
Authors: Hogben C. Adrian M. , Wistrand Per , Maren Thomas H.
Published: December 2017

A significant steady state or d.c. potential difference exists between the cerebrospinal and extracellular fluids of the anesthetized dogfish. Since the cerebrospinal fluid is negative with respect to the extracellular fluid and the chloride concentration is greater in cerebrospinal fluid, the formation of cerebrospinal fluid must involve at least one process: active transport of Cl–. While acetazolamide abolishes the gradient of chloride between dogfish cerebrospinal fluid and plasma, its administration did not demonstrably change the potential difference. Though the active transport of Cl– is clearly part of the process of cerebrospinal fluid formation, it is probably only part of the process. No potential difference was observed between dogfish aqueous humor and extracellular fluid.
Mechanical activity of rat papillary muscle
Authors: Kelly John J. , Hoffman Brian F.
Published: December 2017

Isometric contractions of isolated rat papillary muscles driven at a constant rate have been recorded from paired muscles from hearts of rats 2–6 months of age. At 37°C and a rate of 30/min. tension reaches maximum in 30–60 minutes and then declines slowly during the succeeding 4–12 hours. The maximum tension and the rate of decline with time are related to the diameter of the muscle; however, it has not been possible to demonstrate a definite limit to diameter below which the contraction of the muscle is independent of variations in size. Most factors which increase the force of contraction do not prevent the slow decrease in tension with time. Two exceptions are low temperature (27°C) and high rate (180/min.); under either of these conditions a steady level of tension is maintained for several hours or more. The response of the isolated rat papillary muscle to various physiological alterations is consistent and reproducible if variations in size are considered.
Distribution, migration and binding of whole blood fluoride evaluated with radiofluoride
Authors: Carlson Curtis H. , Armstrong W. D. , Singer Leon
Published: December 2017

A study of the distribution of radiofluoride, between the plasma and erythrocytes of dogs' whole blood showed three-quarters of the radiofluoride in the plasma. The distribution was influenced by carbon dioxide tension associated with the pH of the whole blood. Radiofluoride migrated from plasma to erythrocytes as did chloride when the CO2 tension was increased. Less than 5% of the plasma radiofluoride was bound to plasma solutes under physiological conditions. Radiofluoride binding by bovine plasma albumin was increased by increasing the calcium ion concentration and also by increasing the pH of the solution. The binding of radiofluoride to bovine albumin was affected by the calcium ion concentration. In the synthetic plasma at pH 7.4 the albumin restricted filtration of nearly 40% of the radiofluoride when the calcium ion was elevated to 15 mEq/l. At a calcium ion concentration of 5 mEq/l. the bovine albumin apparently bound 15% of the added radiofluoride. If the albumin were not present there was no restriction of radiofluoride filtration by calcium ion. At pH 6.8 calcium ion concentration of 15 mEq/l. restricted only 3% of the radiofluoride and 5 mEq/l. of calcium had no effect.
Renal excretion of para-aminosalicylic acid: a two-way transport system in the dog
Authors: Huang K. C. , Moore K. B. , Campbell P. C.
Published: December 2017

The renal excretion of free para-aminosalicylic acid (PAS) was studied in dogs. With increasing loading and sustaining infusion of the compound alone, a negative T (rate of urinary excretion minus the rate of filtration of PAS) was observed, but a positive T was obtained during added sodium bicarbonate or sodium acetate infusion. While the positive T values were greater during acetate than in bicarbonate infusion, urinary pH was higher in the latter. Studies with intrarenal arterial injection and stop-flow techniques showed evidence of a bidirectional transport of free PAS. The reabsorption of PAS was influenced by the urinary pH. Sodium bicarbonate infusion reduced the reabsorption; lactic acid infusion increased it. Secretion of the free PAS does not require a high urinary pH and is augmented by acetate and blocked by probenecid. This suggests that the secretion of free PAS involves an active process, analogous, though not necessarily identical to the system for PAH and for other related substances.
A quantitative study of glucagon-induced hepatic glycogenolysis
Authors: Landau Bernard R. , Leonards Jack R. , Barry Frank M.
Published: December 2017

Hepatic vein, portal vein and arterial plasma glucose concentrations, plasma galactose and glucose radioactivity, and hepatic blood flow were measured in dogs following the infusion of galactose-C14 and subsequent glucagon administration. Galactose uptake by the liver was rapid and associated with the release of glucose-C14. Following the glucagon injection there was an immediate release of labeled glucose into the hepatic vein; the peak radioactivity occurring prior to the maximum release of hepatic glucose. With small doses of glucagon small quantities of glucose and radioactivity were released into the circulation. With larger doses of glucagon less radioactivity relative to the quantity of glucose was released. These findings are interpreted to be a consequence of the incorporation of C14 predominantly in the outer tiers of glycogen. The observation of a nearly constant glucose specific activity following insulin administration is discussed as a possible expression of the release of these labeled outer tiers.
Correlation between the surface electrocardiogram and air sac morphology in the White Leghorn rooster
Authors: Douglas Steven D.
Published: December 2017

The morphology of the bird offers a new approach to consideration of the effects of insulation of the heart on the conduction of cardiac potentials to the body surface. The avian heart is insulated cranially and dorsolaterally by large air spaces, which introduce marked inhomogeneities in the volume conductor. Surface electrocardiograms of male White Leghorns were obtained using multiple leads encircling the torso at the levels of the interclavicular joints, ventricle and xiphoid. Magnitude, appearance and duration of the electrocardiographic complexes of 300 leads for each of 15 birds were analyzed. Vectors were plotted for sagittal, horizontal and frontal planes. Low voltage deflections occurred in 46% of the interclavicular leads, 20% of ventricular leads and none of the xiphoid leads. This deflection pattern is due in part to the insulating effect of air sacs between the heart and body surface.
Adaptation to the cardiac necrosis-eliciting effect of stress
Authors: Bajusz Eörs , Selye Hans
Published: December 2017

In rats sensitized with fluorocortisol (F-COL) + Na-acetate, sudden exposure to the stress of intense muscular exercise or forced restraint produces rapidly fatal, severe myocardial necroses. In rats gradually pretreated by repeated short periods of muscular exercise or restraint, even fatal exposure to the same agent produces little or no cardiac necrosis and survival is greatly prolonged. True cross-resistance to the cardiotoxic action of various stressors can be demonstrated under these circumstances, in rats sensitized by F-COL and Na-acetate: the cardiac necrosis-producing effect of muscular exercise could be prevented by pretreatment with cold, that of cold by muscular exercise, that of noradrenaline by restraint, that of restraint by noradrenaline, and that of bone fractures by muscular exercise.
Effects of intra-arterial microbubbles
Authors: Landew Melvin , Bowles L. Thompson , Gelman Sol , Lowenfels Albert B. , Tepper Ronald , Lord Jere W.
Published: December 2017

By means of a partial extracorporeal bypass, incorporating a bubble counting chamber, measured quantities of oxygen and of air microbubbles, having average diameters of 100 and 76 µ, respectively, were introduced into the carotid arteries of dogs. The desired number of bubbles was produced by varying the blood level and gas flow in the bubble oxygenator. Eighty per cent of dogs receiving oxygen in volumes up to 0.43 cc/kg (approximately 12.5 million microbubbles) survived without evidence of neurologic abnormalities. Seventy per cent of the control group, which received no microbubbles, survived. Of those perfused with air, all animals receiving up to 0.19 cc/kg (9.1 million bubbles) survived with no neurologic sequelae. Those perfused with air volumes greater than 0.19 cc/kg died within 24 hours, many exhibiting evidence of neurologic damage. The emphasis upon the introduction of oxygen microbubbles as the major fault of bubble oxygenators may be unwarranted. Air microbubbles are more deleterious than are oxygen microbubbles.
Electrophysiological study of the posterior accessory optic tract
Authors: Hamasaki Duco , Marg Elwin
Published: December 2017

Electrophysiological methods were used to detect the presence of the posterior accessory optic tract—transpeduncular tract in the rabbit. Photic stimulation gave rise to mainly an ‘on’ response from the contralateral nucleus of the transpeduncular tract. Electrical stimulation of the optic nerve fibers evoked a response from this nucleus with a latency of 1–3 msec. A response could not be elicited from the nucleus of the transpeduncular tract, the lateral geniculate nucleus, or the superior colliculus by ipsilateral stimulation. Encéphale isolé preparations showed that the responses recorded under urethane anesthesia were not altered by the drug. The nucleus of the posterior accessory optic tract is situated between the optic nerve and the nucleus of the transpeduncular tract, and lies on the dorsolateral aspect of the midbrain between the superior colliculus and the medial geniculate nucleus. No centrifugal fiber responses have been found which originate from the nucleus of the transpeduncular tract and pass to the retina via the optic nerve.
Renal tubular reabsorption of protein: demonstration and localization of egg albumin and ß-lactoglobulin reabsorption in the dog
Authors: Lathem Willoughby , Davis Bernard B.
Published: December 2017

Using the technique of stop flow analysis, renal tubular reabsorption of egg albumin and ß-lactoglobulin was demonstrated in the dog. The stop flow patterns of these proteins were identical. Both egg albumin and ß-lactoglobulin were shown to be reabsorbed in a proximal part of the nephron overlying the site in which PAH is secreted. Previous studies by stop flow analysis have demonstrated that hemoglobin is reabsorbed in a similar proximal site. These experiments in the intact animal indicate, in agreement with histologic studies, that renal tubular cells have the property of reabsorbing a variety of different types of proteins from glomerular filtrate, and that this property is apparently restricted to cells of the proximal convoluted tubule.
Nonreversibility of the appetitive characteristics of intracranial stimulation
Authors: Brodie David A. , Malis Jerry L. , Moreno Oscar M. , Boren John J.
Published: December 2017

Stainless steel electrodes were implanted in the vicinity of the medial forebrain bundle of monkeys. The monkeys were trained to lever press on an appetitive schedule to receive intracranial stimulation, and on an aversive schedule to avoid a foot shock which was preceded by a warning signal. The lever pressing behavior on the avoidance schedule was extinguished and brain stimulation was substituted as the punishment in the aversive situation. None of the monkeys avoided or escaped the 15-second brain shock. Even when the time period was prolonged to 1 hour, no avoidance behavior occurred. The results indicated that the nature of the intracranial stimulation for the electrode site used was not reversible from appetitive to aversive either with a change in the experimental situation or with a prolongation of the stimulus duration.
Work performance of trained rats as affected by corticoadrenal steroids and by adrenalectomy
Authors: Winter Charles A. , Flataker Lars
Published: December 2017

Fasted rats trained to climb a rope for a food reward were capable of carrying added weights approximately equal to their own body weights. The logclimbing time in seconds was linearly related to the total weight of the animal plus added load within a narrow range of body weight. When correction was made for skeletal muscle mass, the rate of work performance in gram-meters per long second per gram muscle was essentially the same over a wide range of body weights and of added load. Work performance as measured by this preparation was sensitive to changes in glucocorticoid levels, and was increased by cortisone or hydrocortisone in either intact or adrenalectomized animals, and was decreased by adrenal insufficiency.
Some hormonal effects on uptake of free fatty acids by the liver
Authors: Spitzer John J. , McElroy William T.
Published: December 2017

The uptake of free fatty acids (FFA) by the liver was determined in dogs by measuring the portal-hepatic difference in FFA and liver plasma flow. Intravenously administered epinephrine or norepinephrine increased the portal-hepatic difference and the hepatic uptake of FFA. Estimated hepatic plasma flow decreased after norepinephrine, but did not change consistently after epinephrine. Infusion of glucose decreased the portal-hepatic difference and the uptake of FFA by the liver. Insulin diminished hepatic uptake, but the difference was not statistically significant. It is not known, whether the changes in hepatic uptake of FFA are due indirectly to the influence of altered systemic FFA levels on the liver, or to a direct effect of the hormones on the liver.
Relation of route of administration and types of fluid to satisfaction of thirst in the dog
Authors: Holmes Joseph H. , Montgomery Vernon
Published: December 2017

In 13 dogs, using intravenous injection of 20% sodium chloride as a stimulus for inducing a standardized drinking pattern, the substitution for water of various drinking solutions such as 5% glucose, 5% sucrose, 1.8% urea, 1.3% sodium sulfate, 0.9% sodium bicarbonate, 0.85% ammonium chloride, 1.15% sodium acetate and 0.9% magnesium chloride did not alter significantly the total intake. However, with 0.9% sodium chloride the intake averaged 2.4 times that observed for water. Temperature differences of solution did not significantly alter the intake. Introduction of 0.9% sodium chloride, 5% glucose, 1.8% urea and water into the stomach 40 minutes prior to intravenous injection of 20% sodium chloride had an inhibitory effect on drinking response. When similar solutions were given intravenously 40 minutes prior to the salt injection, there was no inhibition of drinking, in fact, the total intake was increased. In these two situations the different drinking response could not be explained by differences in hematocrit or serum concentrations of protein or chloride. Thus, direct introduction of fluids into the blood stream cannot substitute during the 1st hour for the gastric factor in satiation of thirst.
Additive extrarenal effects of small doses of Pitressin and DCA or aldosterone
Authors: Friedman Sydney M. , Nakashima Miyoshi , Friedman Constance L.
Published: December 2017

The rate of rise of blood pressure in DCA-treated rats is accelerated by the concomitant administration of Pitressin tannate in amounts close to the antidiuretic range. This indicates that DCA ordinarily causes compensatory inhibition of the neurohypophysis. The fall in plasma Na which is a characteristic extrarenal effect of Pitressin can be elicited with amounts close to the antidiuretic range in the DCA- or aldosterone-pretreated rat. This accords with the view that the mineralocortex and neurohypophysis are reciprocally linked because both act in the same net direction on ionic equilibrium across the cell membrane.
Osmotic regulation in isolated liver and kidney slices
Authors: Swan A. G. , Miller A. T.
Published: December 2017

Slices of guinea pig liver and kidney cortex were incubated under a variety of metabolic and osmotic conditions and the changes in tissue osmotic pressure and in water and electrolyte distribution were measured. The fresh tissues were approximately isotonic with serum, so that swelling was not due to initially hypertonic cell contents. Autolysis was not an important cause of swelling, probably because of leakage of the autolytic products from the cells. Influx of NaCl was sufficient to account for passage of water into the cells. Based on measured fluxes of sodium, potassium and chloride alone, the water of swelling was isotonic or hypertonic but never hypotonic.
Arteriolar changes in renin tachyphylaxis
Authors: Langford H. G. , Allison Fred
Published: December 2017

Arterioles of the rabbits ear were observed during renin infusion. Initial constriction accompanied the rise in blood pressure. As the blood pressure fell during continued infusion there was concomitant arteriolar relaxation.
High-energy phosphate compounds of rat diaphragm and skeletal muscle fibers
Authors: Peterson Ruth D. , Beatty Clarissa H. , Bocek Rose M.
Published: December 2017

The metabolism of high-energy phosphates in a muscle fiber preparation and diaphragm has been investigated. During dissection the creatine phosphate (CrP) level of fibers decreased but was reconstituted during soaking to 61% of the in situ value and remained uncharged during incubation. Dissection and soaking did not affect the adenosinetriphosphate + adenosinediphosphate (ATP + ADP) levels but incubation caused small decreases. Similar decreases in CrP and ATP levels of diaphragm occurred during incubation. The decreases in the ATP levels in fibers and diaphragm correlated with decreases in adenine absorption. A concomitant shift occurred in the absorption peak of fiber media toward the absorption maximum of hypoxanthine. In contrast, the curves for diaphragm media showed a progressive shift toward the absorption maximum for uric acid. Uricase analyses demonstrated uric acid in diaphragm media. The mesothelial covering of the diaphragm was shown to have a separate and distinct metabolism which converts hypoxanthine to uric acid. Soaking the fibers in iced buffer instead of buffer at room temperature decreased the CrP levels after incubation, ATP values were unaffected.
Humoral nature of hypoglycemia in muscular exercise
Authors: Goldstein M. S.
Published: December 2017

Muscular exercise leads to hypoglycemia. The ‘glucose transport theory’ of insulin action places cellular entry of glucose as the limiting step in its rate of metabolism at rest as well as under exercise. Activation of entry of appropriate sugars by exercise, as a primary event, leads to the augmented rates of glucose metabolism seen with contraction of muscles. The mechanism of hypoglycemia of exercise is shown to be humoral in character. Blood and lymphatic fluid of working dogs, both normal or diabetic, are shown to develop hypoglycemic properties during exercise which can be transferred to resting preparations. This hypoglycemic factor of muscle work is highly labile and appears to be quite distinct from insulin.
Effects of tubular secretion and reabsorption on titration curves of tubular transport
Authors: Weiner I. M. , Garlid Keith D. , Romeo Joseph A. , Mudge Gilbert H.
Published: December 2017

Using standard clearance techniques in the dog with constant rates of urine flow and pH, the tubular transport of four organic acids has been shown to reverse from net secretion at low plasma concentrations to net reabsorption at high. The compounds studied are salicylate, p-hydroxybenzoate, salicylurate and chlorphenol red. The results can not be attributed to an artifact of delay time. This phenomenon can best be interpreted as a consequence of active secretion of a limited capacity and passive back diffusion that does not have a maximal rate. An attempt has been made to evaluate the underlying parameters.
Aldosterone and corticosterone secretion following midbrain transection
Authors: Davis James O. , Anderson Evelyn , Carpenter Charles C. J. , Ayers Carlos R. , Haymaker Webb , Spence William T.
Published: December 2017

Following midbrain transection of six normal dogs, secretion rates for aldosterone, corticosterone and Porter-Silber chromogens were not significantly different from values obtained in unoperated dogs; subsequent bleeding increased aldosterone secretion while corticosterone output was unaltered. In five dogs with thoracic caval constriction in which there was a high secretion of aldosterone, midbrain transection was followed by a reduction in inferior vena caval pressure to a level which was apparently too low to sustain the mechanisms resulting in hyperaldosteronism. In one animal aldosterone and corticosterone output was extremely low despite a high venous pressure. In the two dogs with caval constriction in which the venous pressure remained elevated after midbrain transection, the high rate of aldosterone secretion persisted. Bleeding of dogs with caval constriction and midbrain transection resulted in a striking increase in aldosterone secretion. In dogs with caval constriction, corticosterone secretion (5 dogs) and Porter-Silber chromogen output (4 dogs) were high following midbrain transection, and subsequent bleeding failed to increase corticosterone output. It is concluded that complete midbrain transection does not interfere with the high rate of aldosterone secretion which occurs in response to acute blood loss or following caval constriction if venous pressure is maintained at the high control level.