bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium-mediated activation of pyruvate dehydrogenase in severely injured postischemic myocardium
Authors: Terrand Jerome , Papageorgiou Irene , Rosenblatt-Velin Nathalie , Lerch Rene
Published: December 2017

Indirect evidence suggests that activity of pyruvate dehydrogenase (PDH) influences recovery of the myocardium after transient ischemia. The present study examined the relationship between postischemic injury and activity of PDH and the role of mitochondrial calcium uptake for observed changes in PDH activity. Isovolumically beating isolated rat hearts perfused with erythrocyte-enriched buffer containing glucose, palmitate, and insulin were submitted to either 20 or 35 min of no-flow ischemia. After 20 min of no-flow ischemia, hearts exhibited complete recovery of developed left ventricular pressure (DLVP). The proportion of myocardial PDH in the active state was modestly increased to 38% (compared with 13% in control hearts) without a change in glucose oxidation. In contrast, in hearts subjected to 35 min of no-flow ischemia (which exhibited poor recovery of DLVP), there was marked stimulation of glucose oxidation (+460%; P < 0.01) and pronounced increase in the active fraction of PDH to 72% ( P < 0.01). Glycolytic flux was not significantly altered. Ruthenium red (6 μM) completely abolished the activation of PDH and the increase in glucose oxidation. The results indicate that variable stimulation of glucose oxidation during reperfusion is related to different degrees of activation of PDH, which depends on the severity of the ischemic injury. Activation of PDH seems to be mediated by myocardial calcium uptake.
Decrease in coronary vascular volume in systole augments cardiac contraction
Authors: Willemsen Maurice J. J. M. F. , Duncker Dirk J. , Krams Rob , Dijkman Marieke A. , Lamberts Regis R. , Sipkema Pieter , Westerhof Nico
Published: December 2017

Coronary arterial inflow is impeded and venous outflow is increased as a result of the decrease in coronary vascular volume due to cardiac contraction. We evaluated whether cardiac contraction is influenced by interfering with the changes of the coronary vascular volume over the heart cycle. Length-tension relationships were determined in Tyrode-perfused rat papillary muscle and when coronary vascular volume changes were partly inhibited by filling it with congealed gelatin or perfusing it with a high viscosity dextran buffer. Also, myocyte thickening during contraction was reduced by placing a silicon tube around the muscle. Increasing perfusion pressure from 8 to 80 cmH2O, increased developed tension by ∼40%. When compared with the low perfusion state, developed tension of the gelatin-filled vasculature was reduced to 43 ± 6% at the muscle length where the muscle generates the largest developed tension ( n = 5, means ± SE). Dextran reduced developed tension to 73 ± 6% ( n = 6). The silicon tube, in low perfusion state, reduced the developed tension to 83 ± 7% ( n = 4) of control. Time-control and oxygen-lowering experiments show that the findings are based on mechanical effects. Thus interventions to prevent myocyte thickening reduce developed tension. We hypothesize that when myocyte thickening is prevented, intracellular pressure increases and counteracts the force produced by the contractile apparatus. We conclude that emptying of the coronary vasculature serves a physiological purpose by facilitating cardiomyocyte thickening thereby augmenting force development.
Hypertonic saline method accurately determines parallel conductance for dual-field conductance catheter
Authors: Steendijk Paul , Staal Eva , Jukema J. Wouter , Baan Jan
Published: December 2017

Conversion of conductance catheter data to absolute ventricular volumes requires assessment of parallel conductance ( GP). We determined the accuracy of GPobtained by the hypertonic saline method ( G [Formula: see text]) compared with angiographically derived GP( G [Formula: see text]) and quantified the variabilities of GPfor the dual-field conductance catheter method in nine anesthetized sheep studied at baseline, treated with dobutamine, and subjected to volume loading and β-blockade. G [Formula: see text] and G [Formula: see text] showed an excellent linear correlation ( G [Formula: see text] = 1.002 · G [Formula: see text] + 0.001 Ω−1, R2= 0.92), and Bland-Altman analysis yielded a nonsignificant bias and narrow limits of agreement (bias ± 2SD = 0.002 ± 0.112 Ω−1). Within-animal variability of GPwas very similar with both methods and was due to changes in blood conductivity rather than geometrical changes. Variability between animals was significant (26.3% of mean for G [Formula: see text] and 25.7% for G [Formula: see text]) and thus warrants individual assessment. Variations during the cardiac cycle were not significantly different from zero. With biplane angiography used as gold standard, the hypertonic saline method accurately determines GPfor the dual-field conductance catheter over a wide range of hemodynamic conditions.
Characterization of effects of endothelin-1 on the L-type Ca2+current in human atrial myocytes
Authors: Boixel Christophe , Dinanian Sylvie , Lang-Lazdunski Loîc , Mercadier Jean-Jacques , Hatem Stephane N.
Published: December 2017

The effects of endothelin-1 (ET-1) on the L-type Ca2+current ( ICa) were examined in whole cell patch-clamped human atrial myocytes. Depending on the initial current density, ET-1 (10 nM) increased the amplitude of ICaby 99 ± 7% or decreased it by 33 ± 2%. The stimulatory effect predominated on current of low density (2.3 ± 0.2 pA/pF), whereas ICaof higher density (5.8 ± 0.3 pA/pF) was inhibited by ET-1. After ICastimulation by 1 μM isoproterenol, ET-1 always inhibited the current by 32 ± 7% ( P < 0.05), an effect that was suppressed by pretreating myocytes with pertussis toxin. Atrial natriuretic peptide (ANP) inhibited ICa(41 ± 3%) by reducing intracellular cAMP concentration. In ANP-treated myocytes, the stimulatory effect of ET-1 on ICapredominated (52 ± 7%). The inhibitory effect of ET-1 on ICawas blocked by the ETAantagonist BQ-123, whereas the stimulatory effect was suppressed by the ETBagonist BQ-788. We conclude that ET-1 has opposite effects on ICadepending on the baseline amplitude of current, and both subtype ET receptors are implicated in the signal transduction pathways.
Nitric oxide release during α1-adrenoceptor-mediated constriction of arterioles
Authors: Tuttle Jay L. , Falcone Jeff C.
Published: December 2017

We examined endothelial modulation of norepinephrine (NE)-mediated constriction in isolated, cannulated, first-order arterioles from skeletal muscle of rats. Acute arteriolar constrictor responses to NE (10−9 to 10−7 M) were significantly ( P < 0.05) enhanced after either endothelial denudation or inhibition of nitric oxide synthase with N G-monomethyl-l-arginine (10−4 M, 30 min). In contrast, arteriolar constrictions to NE were not different after treatment with either the cyclooxygenase inhibitor diclofenac (10−6 M, 30 min) or the K+-channel blocker tetrabutylammonium (5 × 10−5 M, 30 min). We also measured arteriolar responses to the vasoconstrictor PGF2α; responses were not altered by any of the experimental treatments, which indicates that this phenomenon is not ubiquitous to all vasoconstricting agents. Mechanistically, we examined vascular smooth muscle (VSM) and endothelial cell calcium. Both NE and PGF2α significantly increased VSM cell calcium measurements; however, endothelial cell calcium was significantly increased with NE or phenylephrine (an α1-adrenergic agonist) but not with PGF2αor UK-14304 (an α2-adrenergic agonist). Together these findings suggest that in rat cremaster first-order arterioles, NE stimulates an increase in VSM calcium via adrenergic receptors with subsequent increase in endothelial cell calcium, possibly via stimulation of α1-adrenergic receptors on the arteriolar endothelium. The burst in endothelial cell calcium may then lead to the production of nitric oxide, which diffuses to the VSM, attenuates constriction, and maintains at least some minimal level of blood flow.
Cyclooxygenase-2 does not mediate late preconditioning induced by activation of adenosine A1 or A3receptors
Authors: Kodani Eitaro , Shinmura Ken , Xuan Yu-Ting , Takano Hitoshi , Auchampach John A. , Tang Xian-Liang , Bolli Roberto
Published: December 2017

Recent studies have demonstrated that the adenosine A1 receptor agonist 2-chloro- N 6-cyclopentyladenosine (CCPA) and the adenosine A3 receptor agonist N 6-(3-iodobenzyl)adenosine-5′- N-methyluronamide (IB-MECA) produce a delayed phase of protection against infarction similar to the late phase of ischemic preconditioning (PC). However, the mechanism for adenosine A1 or A3receptor-induced late PC remains unknown. The goal of this study was to determine whether the delayed cardioprotective effects of adenosine A1 or A3 receptors are mediated by cyclooxygenase-2 (COX-2), which is an obligatory mediator of ischemic PC. We found that COX-2 protein expression (Western blotting) did not increase 24 h after the administration of either CCPA (100 μg/kg iv) or IB-MECA (300 μg/kg iv) compared with controls. To probe the role of constitutive COX-2 expression, conscious rabbits were subjected to 30-min coronary occlusion followed by 72-h reperfusion. Twenty-four hours before the occlusion, the rabbits were pretreated with CCPA (100 μg/kg iv) or IB-MECA (300 μg/kg iv). Both CCPA and IB-MECA resulted in a marked (∼47%) reduction in infarct size vs. controls [36.2 ± 4.0% of the risk region ( n = 9), 31.2 ± 4.7% ( n = 9), and 59.5 ± 3.8% ( n = 9), respectively; P < 0.05], similar to that induced by the late phase of ischemic PC [31.8 ± 3.2% ( n = 9)]. The selective COX-2 inhibitor N-(2-[cyclohexyloxy]4-nitrophenyl)methanesulfonamide (NS-398, 5 mg/kg), which abolished the protective effect of ischemic late PC, failed to block the protection of either CCPA or IB-MECA, indicating that COX-2 does not mediate the delayed protection of either CCPA or IB-MECA [CCPA + NS-398, 29.1 ± 3.4% ( n = 7); IB-MECA + NS-398, 34.9 ± 2.9% ( n = 8)]. NS-398 in itself did not affect infarct size [54.9 ± 3.7% ( n = 9)]. Taken together, these results demonstrate that, in contrast to ischemia-induced late PC, the mechanisms of adenosine A1 or A3 receptor-induced late PC is independent of COX-2.
Smaller age-associated reductions in leg venous compliance in endurance exercise-trained men
Authors: Monahan Kevin D. , Dinenno Frank A. , Seals Douglas R. , Halliwill John R.
Published: December 2017

We determined the independent and interactive influences of aging and habitual endurance exercise on calf venous compliance in humans. We tested the hypotheses that calf venous compliance is 1) reduced with age in sedentary and endurance-trained men, and 2) elevated in young and older endurance-trained compared with age-matched sedentary men. We studied 8 young (28 ± 1 yr) and 8 older (65 ± 1) sedentary, and 8 young (27 ± 1) and 8 older (63 ± 2) endurance-trained men. Calf venous compliance was measured in supine subjects by inflating a venous collecting cuff, placed above the knee, to 60 mmHg for 8 min and then decreasing cuff pressure at 1 mmHg/s to 0 mmHg. Calf venous compliance was determined using the first derivative of the pressure-volume relation during cuff pressure reduction (compliance = β1 + 2 · β2 · cuff pressure). Calf venous compliance was reduced with age in sedentary (∼40%) and endurance-trained men (∼20%) (both P < 0.01). Furthermore, calf venous compliance was ∼70–120% greater in endurance-trained compared with age-matched sedentary men and ∼30% greater in older endurance-trained compared with young sedentary men (both P < 0.01). These data indicate that calf venous compliance is reduced with age in sedentary and endurance-trained men, but compliance is better preserved in endurance-trained men.
Mitochondrial KATPchannel activation reduces anoxic injury by restoring mitochondrial membrane potential
Authors: Xu Meifeng , Wang Yigang , Ayub Ahmar , Ashraf Muhammad
Published: December 2017

Mitochondrial membrane potential (ΔΨm) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K+(mitoKATP) channel activation prevents the collapse of ΔΨmin myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos and in an electron microscope and exhibited a collapsed ΔΨm, as monitored by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome cimmunostaining. Activation of mitoKATPchannel with diazoxide (100 μmol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized ΔΨm. This protection was blocked by 5-hydroxydecanoate (500 μmol/l), a mitoKATPchannel-selective inhibitor, but not by HMR-1098 (30 μmol/l), a putative sarcolemmal KATPchannel-selective inhibitor. Dissipation of ΔΨmalso leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts ΔΨmand induces apoptosis, which are prevented by the activation of the mitoKATPchannel. This further emphasizes the therapeutic significance of mitoKATPchannel agonists in the prevention of ischemia-reperfusion cell injury.
Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins
Authors: Hamilton Karyn L. , Powers Scott K. , Sugiura Takao , Kim Sunjoo , Lennon Shannon , Tumer Nihal , Mehta Jawahar L.
Published: December 2017

We examined the effects of 3 days of exercise in a cold environment on the expression of left ventricular (LV) heat shock proteins (HSPs) and contractile performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were divided into the following three groups ( n = 12/group): 1) control, 2) exercise (60 min/day) at 4°C (E-Cold), and 3) exercise (60 min/day) at 25°C (E-Warm). Left anterior descending coronary occlusion was maintained for 20 min, followed by 30 min of reperfusion. Compared with the control group, both the E-Cold and E-Warm groups maintained higher ( P < 0.05) LV developed pressure, first derivative of pressure development over time (+dP/d t), and pressure relaxation over time (−dP/d t) throughout I/R. Relative levels of HSP90, HSP72, and HSP40 were higher ( P < 0.05) in E-Warm animals compared with both control and E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts ( P < 0.05). Protection against I/R-induced lipid peroxidation in the LV paralleled the increase in MnSOD activity whereas lower levels of lipid peroxidation were observed in both E-Warm and E-Cold groups compared with control. We conclude that exercise-induced myocardial protection against a moderate duration I/R insult is not dependent on increases in myocardial HSPs. We postulate that exercise-associated cardioprotection may depend, in part, on increases in myocardial antioxidant defenses.
Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?
Authors: Katusic Zvonimir S.
Published: December 2017

Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS catalytic activity is not completely understood. Existing evidence suggests that it can act as alosteric and redox cofactors. Suboptimal concentration of tetrahydrobiopterin reduces formation of nitric oxide and favors “uncoupling” of NOS leading to NOS-mediated reduction of oxygen and formation of superoxide anions and hydrogen peroxide. Recent findings suggest that accelerated catabolism of tetrahydrobiopterin in arteries exposed to oxidative stress may contribute to pathogenesis of endothelial dysfunction present in arteries exposed to hypertension, hypercholesterolemia, diabetes, smoking, and ischemia-reperfusion. Beneficial effects of acute and chronic tetrahydrobiopterin supplementation on endothelial function have been reported in experimental animals and humans. Furthermore, it appears that beneficial effects of some antioxidants (e.g., vitamin C) on vascular function could be mediated via increased intracellular concentration of tetrahydrobiopterin. In this review, the potential role of tetrahydrobiopterin in the pathogenesis of vascular endothelial dysfunction and mechanisms underlying beneficial vascular effects of tetrahydrobiopterin will be discussed.
Vasoactive factors and growth factors alter vascular smooth muscle cell EC-SOD expression
Authors: Strålin Pontus , Marklund Stefan L.
Published: December 2017

Oxygen free radicals have been suggested to play important roles in atherogenesis and other pathological processes in the blood vessel wall. The vascular wall contains large amounts of extracellular superoxide dismutase (EC-SOD), which is produced and secreted to the extracellular space by smooth muscle cells. In this study, we investigated the influence of factors regulating tension and proliferation of vascular smooth muscle cells and of some interstitial matrix components on EC-SOD expression. The expression and secretion of EC-SOD were upregulated by histamine, vasopressin, oxytocin, endothelin-1, angiotensin II, serotonin, heparin, and heparan sulfate and were downregulated by platelet-derived growth factors-AA and -BB, acidic and basic fibroblast growth factors, and epidermal growth factor. The responses were slow and developed over several days. The findings suggest that various physiological and pathological conditions might markedly influence EC-SOD expression, significantly altering the susceptibility of the vascular wall to effects of the superoxide radical.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a nicotine derivative, induces apoptosis of endothelial cells
Authors: Tithof Patricia K. , Elgayyar Mona , Schuller Hildegard M. , Barnhill Maryann , Andrews Richard
Published: December 2017

Smoking causes endothelial cell (EC) injury; however, neither the components of cigarette smoke nor the mechanisms responsible for this injury are understood. The nitrosated derivative of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), has been implicated in the carcinogenic effects of tobacco; however, the effects of NNK on the cardiovascular system are largely unknown. NNK binds to β1- and β2-adrenergic receptors. Because β-adrenergic receptor activation causes arachidonic acid (AA) release and cellular injury, we postulated that NNK causes EC injury by a mechanism that involves β-adrenergic-mediated release of AA. NNK stimulated [3H]AA release from ECs, and this effect was mediated by both β1- and β2-adrenergic receptors because pretreatment with atenolol or ICI 118,551 inhibited the response. NNK also induced EC apoptosis, as measured by terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling and annexin V staining. NNK-mediated apoptosis was attenuated by pretreatment with atenolol or ICI 118,551. Furthermore, depletion of cellular AA by incubation with eicosapentaenoic acid abolished the apoptotic effect of NNK. These data suggest that NNK causes EC apoptosis by a mechanism that involves β1- and β2-adrenergic receptor-mediated release of AA.
A mathematical model of CO2 effect on cardiovascular regulation
Authors: Magosso Elisa , Ursino Mauro
Published: December 2017

The effect of changes in arterial CO2tension on the cardiovascular system is analyzed by means of a mathematical model. The model is an extension of a previous one that already incorporated the main reflex and local mechanisms triggered by O2 changes. The new aspects covered by the model are the O2-CO2 interaction at the peripheral chemoreceptors, the effect of local CO2 changes on peripheral resistances, the direct central neural system (CNS) response to CO2, and the control of central chemoreceptors on ventilation and tidal volume. A statistical comparison between model simulation results and various experimental data has been performed. This comparison suggests that the model is able to simulate the acute cardiovascular response to changes in blood gas content in a variety of conditions (normoxic hypercapnia, hypercapnia during artificial ventilation, hypocapnic hypoxia, and hypercapnic hypoxia). The model ascribes the observed responses to the complex superimposition of many mechanisms simultaneously working (baroreflex, peripheral chemoreflex, CNS response, lung-stretch receptors, local gas tension effect), which may be differently activated depending on the specific stimulus under study. However, although some experiments can be reproduced using a single basal set of parameters, reproduction of other experiments requires a different combination of the mechanism strengths (particularly, a different strength of the local CO2mechanism on peripheral resistances and of the CNS response to CO2). Starting from these results, some assumptions to explain the striking differences reported in the literature are presented. The model may represent a valid support for the interpretation of physiological data on acute cardiovascular regulation and may favor the synthesis of contradictory results into a single theoretical setting.
Activation of PKC decreases myocardial O2consumption and increases contractile efficiency in rats
Authors: Noguchi Teruo , Chen Zengyi , Bell Stephen P. , Nyland Lori , LeWinter Martin M.
Published: December 2017

The effect of protein kinase C (PKC) activation on cardiac mechanoenergetics is not fully understood. To address this issue, we determined the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on isolated rat hearts. Hearts were exposed to PMA with or without pretreatment with the PKC inhibitor chelerythrine. Contractile efficiency was assessed as the reciprocal of the slope of the linear myocardial O2consumption (V˙o2) pressure-volume area (PVA) relation. PMA decreased contractility ( Emax; −30 ± 8%; P < 0.05) and increased coronary perfusion pressure (+58 ± 11%; P < 0.01) without altering left ventricular end-diastolic pressure. Concomitantly, PMA decreased PVA-independentV˙o2[nonmechanical energy expenditure for excitation-contraction (E-C) coupling and basal metabolism] by 28 ± 8% ( P < 0.05) and markedly increased contractile efficiency (+41 ± 8%; P < 0.05) in a manner independent of the coronary vascular resistance. Basal metabolism was not affected by PMA. Chelerythrine abolished the PMA-induced vasoconstriction, negative inotropy, decreased PVA-independent V˙o2, and increased contractile efficiency. We conclude that PKC-mediated phosphorylation of regulatory proteins reduces V˙o2via effects on both the contractile machinery and the E-C coupling.
Mechanisms mediating NTS P2x receptor-evoked hypotension: cardiac output vs. total peripheral resistance
Authors: Kitchen Amy M. , Collins Heidi L. , DiCarlo Stephen E. , Scislo Tadeusz J. , O'Leary Donal S.
Published: December 2017

We have previously shown that P2x purinoceptor activation in the subpostremal nucleus tractus solitarius (NTS) produces dose-dependent decreases in mean arterial pressure (MAP), heart rate, efferent sympathetic nerve activity, and significant peripheral vasodilation. However, the relative roles of cardiac output (CO) and total peripheral resistance (TPR) in mediating this depressor response are unknown. Bradycardia does not necessarily result in decreased CO, because, with the greater filling time, stroke volume may increase such that CO may be unchanged. We measured changes in CO (via a chronically implanted flow probe on the ascending aorta) and MAP in α-chloralose- and urethane-anesthetized male Sprague-Dawley rats in response to microinjection of the selective P2x purinoceptor agonist α,β-methylene ATP (25 and 100 pmol/50 nl) into the subpostremal NTS. TPR was calculated as MAP/CO. At the low dose of NTS P2x purinoceptor agonist, the reduction in MAP was primarily mediated by reductions in TPR (−31.3 ± 3.3%), not CO (−8.7 ± 1.7%). At the high dose, both CO (−34.4 ± 6.6%) and TPR (−40.2 ± 2.5%) contribute to the reduction in MAP. We conclude that the relative contribution of CO and TPR to the reduction in MAP evoked by NTS P2x purinoceptor activation is dependent on the extent of P2x purinoceptor activation.
Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system
Authors: Leenen Frans H. H. , White Roselyn , Yuan Baoxue
Published: December 2017

To assess the possible contribution of the circulatory and cardiac renin-angiotensin system (RAS) to the cardiac hypertrophy induced by a β-agonist, the present study evaluated the effects of isoproterenol, alone or combined with an angiotensin I-converting enzyme inhibitor or AT1 receptor blocker, on plasma and LV renin activity, ANG I, and ANG II, as well as left ventricular (LV) and right ventricular (RV) weight. Male Wistar rats received isoproterenol by osmotic minipump subcutaneously and quinapril or losartan once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassay after separation by HPLC. Isoproterenol alone decreased blood pressure, more markedly when combined with losartan or quinapril. Isoproterenol significantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented the increase in RV collagen but enhanced the increase in LV collagen. Isoproterenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isoproterenol combined with losartan or quinapril, caused marked further increases except for a significant decrease in plasma ANG II with quinapril. Isoproterenol alone did not increase LV ANG II and, combined with losartan or quinapril, actually decreased LV ANG II. These results indicate that isoproterenol-induced cardiac hypertrophy is associated with clear increases in plasma ANG II, but not in LV ANG II. Both losartan and quinapril lower LV ANG II below control levels, but do not prevent the isoproterenol-induced cardiac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to β-receptor stimulation.
Nutritive blood flow affects microdialysis O/I ratio for [14C]ethanol and3H2O in perfused rat hindlimb
Authors: Newman John M. B. , Di Maria Carla A. , Rattigan Stephen , Clark Michael G.
Published: December 2017

Changes in the microdialysis outflow-to-inflow (O/I) ratio for [14C]ethanol and3H2O were determined in the perfused rat hindlimb after increases and decreases in nutritive flow mediated by the vasoconstrictors norepinephrine (NE) and serotonin (5-HT), respectively. Microdialysis probes (containing 10 mM [14C]ethanol and 3H2O pumped at 1 or 2 μl/min) were inserted through the calf of the rat. Hindlimb perfusion flow rate was varied from 6 to 56 ml · min−1 · 100 g−1 in the presence of NE, 5-HT, or saline vehicle. The O/I ratios for both tracers were determined at each perfusion flow rate, as was perfusion pressure, oxygen uptake (a surrogate indicator of nutritive flow), and lactate release. Both tracers showed a decreased O/I ratio as hindlimb perfusion flow was increased, with [14C]ethanol being higher than 3H2O. NE decreased the O/I ratio compared with vehicle, and 5-HT increased it for both tracers and both microdialysis flow rates. We conclude that the microdialysis O/I ratio, while able to detect changes in total flow, is also sensitive to changes in nutritive and nonnutritive flow, where the latter still extracts tracer, but less than the former.
Alteration of adrenergic responses by chronic cholinergic blockade
Authors: Jerram David C.
Published: December 2017

The effect of the chronic administration of cholinergic blocking agents on the secretory and cardiovascular responses to epinephrine, levarterenol and isoproterenol has been determined in the dog. Chronic cholinergic blockade (CCB) produced a supersensitivity of the submaxillary gland to epinephrine and levarterenol as has been shown previously. Isoproterenol was found to have a profound secretory effect on the submaxillary gland of the dog. During CCB, the volume of secretion produced by isoproterenol was greatly increased. Changes in systolic and diastolic blood pressure, cardiac output, peripheral resistance, heart rate and duration of systole produced by graded doses of epinephrine, levarterenol and isoproterenol were not significantly or systematically altered by CCB. It was concluded that CCB does not alter the sensitivity of the vasculature to adrenergic agents. In 12 of 13 dogs, the heart rate after acute atropinization was significantly lower during CCB than in the control experiments.
Species differences in platelet agglutination in man and in the dog, swine and rabbit
Authors: LeRoy E. Carwile , Mason R. G. , Brinkhous Kenneth M.
Published: December 2017

The in vitro agglutination of platelets by incubated plasma-cation mixtures was studied in man and in the dog, swine and rabbit. A macroscopic agglutination test previously described was used. In homologous tests TAg activity was demonstrated in swine and in the dog. TAg is a thrombocyte agglutinating factor not adsorbed by BaSO4 and active with Mg++ and Mn++. In all species agglutination also occurred with Ca++ and whole plasma; in the dog and in man this activity was removed from plasma by BaSO4 adsorption, and in the dog was recovered in the eluate. This agglutinating factor is tentatively designated TAg'. In the rabbit and in swine, platelets were agglutinated with adsorbed plasma and Ca++ From studies with heterologous mixtures of plasma and platelets, it was concluded that the platelet rather than the plasma determines species differences in cation requirements and agglutinability. All plasmas studied cause platelet agglutination characteristic of the platelet species if appropriate cations are present. Porcine plasma appears to contain a heterophil antibody for human platelets.
Thyroid function in various strains of mice: T/S ratio, PBI and thyroid weight
Authors: Silverstein Emanuel , Sokoloff Leon , Mickelsen Olaf , Jay George E.
Published: December 2017

Strain differences were observed in the T/S ratios and thyroid weights of 505 mice comprising six inbred strains and three pairs of F1 hybrids. These differences were not accounted for by variations in body weight or degree of blocking of iodine incorporation into organic compounds by Tapazole. There was an apparently inverse relationship between the mean T/S ratios of the various strains and the relative weights of the thyroid glands. The weights of the thyroid glands increased progressively from 7 to 16 months of age in each strain even though there were only small changes in body weight. The T/S ratios were relatively unchanged between these ages. The weight of the thyroid gland appeared to be influenced by the interaction between the strain of animal, diet fed and possibly by obesity. The mean plasma PBI values ranged from 0.9 to 3.5 µg/ml and showed no relationship to the T/S ratios.
Effect of sodium nitroprusside on blood pressure responses to histamine
Authors: Hilton James G. , Tumlinson William B.
Published: December 2017

Effects of decrease in tone produced by sodium nitroprusside on blood pressure responses to histamine were studied in dogs anesthetized with sodium pentobarbital. A series of graded doses of l-histamine acid phosphate was given before and during infusion of sodium nitroprusside (three levels: 2,5 and 8 µg/kg/min.) and blood pressure responses to each dose of the administered histamine were recorded. Blood pressure records were analyzed in terms of minimum blood pressure attained, actual fall in blood pressure and duration of fall in blood pressure before and during the infusion. There was a significant reduction in the fall in blood pressure, but no significant change in the duration of the depressor response. The amount of reduction in minimum attained blood pressure decreased as the size of the dose of histamine increased. This together with the decrease in fall in blood pressure seems to indicate that decrease in blood vessel tone by the prior administration of sodium nitroprusside antagonizes the depressor response of histamine. The extent of this antagonism is such that the minimum obtainable blood pressure with maximum doses of histamine is unchanged by the infusion of sodium nitroprusside.
Transmembrane potentials and atrial fibrillation
Authors: Klein Richard L. , Holland William C.
Published: December 2017

The mean maximum following frequency of single atrial cells as determined by the microelectrode technique was found to be 820/min. with a range of 600–1050. The mean ‘firing’ rate of atrial cells during acetylcholine induced fibrillation was 900/min. with a range of 600–1250/min. The data are interpreted to mean that the observed changes in ion transport during fibrillation are not the result of higher firing rates of atrial cells as compared to those during rapid electrical excitation.
Effect of mersalyl on isolated perfused guinea pig atria
Authors: Stein Edward , Magin John , Kleinfeld Morris
Published: December 2017

The effects of mersalyl in concentrations of 0.4–2 x 10–4 m were studied on isolated perfused guinea pig atria. Mersalyl produced a moderate slowing of the heart rate, an enhanced repolarization of the transmembrane potential and a decrease in contractility of both right and left atrium. The atria eventually developed asystole which usually occurred earlier in the left than in the right atrium. Administration of 6.3 x 10–4 m cysteine hydrochloride as a constant perfusion reversed the asystole. The improvement in both the electrical and mechanical activities occurred gradually. The mechanism of action of mersalyl is attributed to inhibition of certain protein sulfhydryls in the cell; the reactivation of function by cysteine is postulated to be due to the formation of mersalyl cysteinate.
Complete occlusion of a renal artery branch on glomerular and tubular function
Authors: Blake William D.
Published: December 2017

Experiments were made on anesthetized, laparotomized dogs to define alterations in glomerular and tubular function occurring when a branch of the left renal artery is occluded. Diuresis was induced by intravenous infusion of glucose, NaCl or urea solutions. Branch-artery occlusion on the left induced variable increases in filtration rate/tubule on the left only and increased fraction of filtered water excreted (V/Ccr) from both kidneys except when the left kidney was denervated during operative preparation. V/Ccr increased whether or not filtration/tubule increased. Branch-artery occlusion distorted the usual relationship between urine solute concentration and urine flow but not between urine solute concentration and V/Ccr, indicating that increased urine flow/tubule was osmotically induced and not a water diuresis. Thus, reduction of functional renal mass from branch-artery occlusion, frequently and inexplicably increased filtration/tubule in the ipsilateral kidney and independently initiated bilateral decrease in solute and water reabsorption that may have been mediated via the sympathetic nervous system.
Changes in intestinal volume with hemorrhage
Authors: Johnson Paul C.
Published: December 2017

The purpose of these experiments was to study the changes in intestinal volume occurring with hemorrhage, utilizing a gravimetric technique which permitted a study of small segments of the intestine. It had been observed previously that intestinal weight often increased in the upper small intestine during hemorrhage, while in the lower small intestine it usually decreased. In studying the latter effect it was found that sympathetic nerve activity and reduction of venous pressure were both important in decreasing intestinal volume. Changes in tonus and local reduction in arterial pressure did not appear to be important. The increase in volume with hemorrhage appeared due to epinephrine discharge from the adrenal medulla since it was eliminated by adrenalectomy. Local pressure changes and alteration of tonus were eliminated as causal factors. It appears that systemic hypotension induces sympathetic discharge which in turn may cause either an increase or a decrease in intestinal blood volume. Sympathetic discharge over the vasoconstrictor fibers reduces blood volume while adrenal medullary secretion increases it. The observed response is apparently a resultant of these two antagonistic effects.
Effects of antral acidification and atropine on histamine-induced gastric secretion in dogs
Authors: Shapira Daniel , Morgenstern Leon , State David
Published: December 2017

To determine whether acid in the gastric antrum causes inhibition of HCl secretion in the fundus of the stomach, five dogs were prepared with antral and fundic pouches. In one animal these pouches had intact vagal innervation. In each experiment a small dose of histamine was administered at a constant rate for 5–6 hours. After the rate of HCl output from the fundic pouch leveled off, the antral pouch was perfused with acid for 3 hours. During this period the rate of HCl output sometimes fell below preperfusion level, but similar results were obtained without antral perfusion. The findings in 30 tests and 30 controls failed to suggest that antral acidification influenced the fundic secretion. In a parallel study, 2 mg of atropine produced marked inhibition of secretion, proving that true inhibitory effects were demonstrable with the methods employed. These findings raise doubt that the acidified antrum produces an antisecretory hormone or that it can inhibit fundic secretion via a vagal reflex.
Cell, plasma and bleeding volume in the dog after rapid hemorrhage and reinfusion
Authors: Huggins R. A. , Deavers S. , Smith E. L.
Published: December 2017

Cell, plasma volume, hematocrits, protein concentrations and bleeding volumes were recorded in control, overtransfused, hypo- and hyperthermic dogs. The animals were bled rapidly to approximately 0 mm Hg and reinfused three times with determinations between each successive hemorrhage. For the control group the bleeding volume in cubic centimeters per kilogram and percentage of blood volume decreased significantly with each successive bleeding. The dogs receiving a transfusion of 81 cc/kg of blood lost 22.8 cc/kg of plasma as a result of the overtransfusion. At the end of the final hemorrhage 6.3 cc/kg of cells and 14.4 cc/kg of additional plasma was unaccounted for and while the cc/kg bleeding volume increased markedly it represented the same portion of the blood volume (50%) as in the control group. Hypo- and hyperthermia did not produce a significant change in any of the parameters. However these groups did not tolerate the hemorrhages as well, the number of dogs dying increased with successive bleedings.
Effects of corticosteroids on electrolyte metabolism during osmoregulation in teleosts
Authors: Edelman Isidore S. , Young Ho Lee , Harris John B.
Published: December 2017

The effects of injections of hydrocortisone, 9 α fluorohydrocortisone and d, l aldosterone on rates of loss of Na and K and on serum and muscle electrolyte concentrations were studied in euryhaline and stenohaline marine teleosts during immersion in fresh water for periods of 1–16 hours. Survival time was not affected by administration of adrenal steroids. Survival in fresh water was inversely correlated to the rates of Na loss. Administration of corticosteroids had no consistent effect on either Na or K loss or on the changes in plasma or muscle electrolyte content during immersion in fresh water. It is inferred from the data that euryhalinity depends on the ability to conserve Na, K and Cl in hypotonic water and that NaCl depletion, extracellular fluid contraction and hypovolemia are major factors in the failure of marine teleosts to survive in fresh water.
Effect of seizures in visual cortex on response to geniculate stimulation
Authors: Vastola E. F. , Rosen A.
Published: December 2017

Electrical seizures elicited in the visual cortex of unanesthetized cats by direct cortical stimulation have been found to be associated with two phases of depression of the primary response evoked by single stimuli to the visual radiation fibers at their origin in the lateral geniculate body. Depression in the first phase, accompanying what has been called the after-discharge proper, was relatively small and probably in large measure the result of tetanization of the visual radiation fiber terminals. It is suggested, therefore, that the primary response and the after-discharge utilize different portions of the cortical circuitry. Depression in the later phase coincided with the appearance of grouped bursts of irregular spikes and slow waves, was of severe degree, and lasted several minutes. Depression of the radiation spike was prominent during this phase if the seizure was long. This phase has been identified with the spreading depression of previous investigators and was shown to depend, in part at least, upon the seizure itself and not simply upon the direct effects of the tetanic stimulating current.
Heparin and nitrogen excretion in normal rats
Authors: Granitsas A. N.
Published: December 2017

The injection of heparin to normal rats causes a decreased nitrogen excretion. This effect compared to the action of 2.5 units of growth hormone under the same conditions, appears to be similar but not identical. Protamine produces an increased nitrogen excretion and abolishes the action of heparin.
Effect of gamma-aminobutyric acid on pulmonary stretch receptors in the cat
Authors: Drakontides Anna B.
Published: December 2017

Studies on the effect of γ-aminobutyric acid (GABA) on slowly adapting pulmonary stretch receptors of the cat revealed a decrease in sensitivity to stretch, as evidenced by a reduction in firing during inflation of the lungs following drug administration. This phenomenon was characterized by a nonlinear dose effect relationship, a definite effect being observed at 0.1 mg/kg i.v. While immediate respiratory responses to GABA were clearly unrelated to its effect on afferent impulses from the lungs, the increase in depth of respiration following the initial apnea is consistent with desensitization of pulmonary stretch receptors. Further characterization of the effects observed were attempted by studying antagonism of GABA to protoveratrine.
Blood eosinophil rhythm in the hamster
Authors: Halberg Franz , Chaudhry Anand P.
Published: December 2017

In the absence of stimulation other than daily routine, Syrian golden hamsters show 24-hour periodic changes in eosinophil count. Animals standardized on a regimen providing for light from 0600 to 1800 alternating with 12 hours darkness, have high eosinophil levels around noon and lower ones around midnight. The timing of hamster eosinophil rhythm corresponds to that recorded earlier for other nocturnal mammals, being out of phase by about 12 hours with the timing of the same rhythm in diurnally active species.
Transfer of homologous thoracic duct lymphocytes to irradiated rats
Authors: Anderson D. O. , Whitelaw D. M.
Published: December 2017

Lymphocytes from the thoracic duct of rats were injected intraperitoneally into homologous rats previously exposed to 900 rads of total body radiation. Repeated white blood cell counts, platelet counts and polychromatophilia and reticulocyte counts provided no evidence that the transplanted cells were able to repopulate the bone marrow.
Effect of parathyroid extract on citrate metabolism in bone
Authors: Lekan Eugene C. , Laskin Daniel M. , Engel Milton B.
Published: December 2017

In studies on the citrate metabolism of bone it has not been possible to distinguish the relatively inert extracellular citrate from the more labile intracellular part. To deal with this problem, the conversion of C14-labeled sodium pyruvate to citrate was studied in metaphyseal bone slices from normal rabbits and from a group in which bone resorption was produced by parathyroid extract. Under the influence of parathyroid extract there was approximately twice as much radioactive citrate present. This citrate is then available to react with bone matrix to form soluble compounds with calcium, withdrawing this cation from the bone salts and its protein-bound complexes.
Corticosterone in mouse adrenal in relation to sex and heterotopic pituitary isografting
Authors: Halberg Franz , Haus Erhard
Published: December 2017

In two populations of mice, one inbred (C, Bag albino), the other hybrid, adrenal ‘corticosterone’ levels determined at time of peak physiologic secretion differed consistently between the two sexes. The female glands, heavier than those of males, had the higher content and concentration of ‘corticosterone.’ In female C and D8 (Dilute Brown, subline 8) mice, adrenal ‘corticosterone’ content is further elevated during a period from about 64 to about 180 days after pituitary isografting; i.e. many months prior to the appearance of breast cancers, induced or enhanced in these stocks by the heterotopic pituitary.
Intestinal absorption of coprostanol (coprosterol) in the rat
Authors: Setty C.S. Narayana , Ivy A. C.
Published: December 2017

A basal sterol-free diet consisting of casein, 18%; dextrin, 57%; oleic acid, 9%; U.S.P. salt mixture, 2%; yeast, 5%; and cellulose, 9%; along with 1% sulfasuxidine and 0.2% streptomycin sulfate was fed to eight rats during a control period of 12 days, the feces being collected under alcohol the last 4 days and assayed for digitonide sterol. The experiment was repeated with the addition of 28 mg of coprostanol to the diet. It was found that from 41 to 61% (average 48%) of the coprostanol was absorbed. The relation of chemical structure to the absorbability of cholesterol derivatives is discussed with the finding that all absorbable cholesterol derivatives have the ‘chair’ conformation, but are not alike in digitonide formation and Liebermann-Burchard color reaction.
Effect of acid and alkaline K phosphate on acid and electrolyte excretion in dogs
Authors: Brodsky William A. , Carrasquer Gaspar
Published: December 2017

Acidic or buffered potassium phosphates, given i.v. to dogs, induced increases of excretion of potassium, phosphate and of sodium. Maximal values of excretion were 865 µmoles/min/m2 for phosphate, 760 for potassium, 283 for titratable acid and 622 for sodium. Titratable acid increased after KH2PO4 and remained constant after K2HPO4-KH2PO4 (pH 7.4). Then, a technique of adding K+ without changing osmotic or phosphate load of infusion fluid was used. Acidic, buffered or dibasic potassium phosphates were substituted stoichiometrically for buffered sodium phosphate during periods of excretion of titratable acid at levels of 250–450 µmoles/min. After K+ substitution, excretion of sodium decreased before that of K+ changed. Then excretion of K+ increased while that of Na and phosphate remained fixed. Excretion of titratable acid increased in parallel with that of K+ after KH2PO4 and remained constant after K2HPO4. Excretion of titratable acid decreased while that of K+ increased after substitution of buffered potassium phosphate. Plasma CO2 content remained constant or increased after K+ substitution. Data could be explained on the basis of a tubular system of anion (H2PO4–) secretion, as well as on the basis of K+-H+ ion exchange for Na+ reabsorption.
Effects of cold stress on mitochondrial oxidative phosphorylation
Authors: Patkin Judith , Masoro E. J.
Published: December 2017

Page 202: Judith Patkin and E. J. Masoro, "Effects of cold stress on mitochondrial oxidative phosphorylation." Footnote to tables 1 and 2 should read: Values are means ± standard deviation of the mean.