bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of immunological sensitization on the responses and sensitivity of guinea pig airways to bronchoconstrictors. Modulation by selective inhibition of arachidonic acid metabolism
Authors: Saad Maan H. , Burka John F.
Published: April 2011

The force generated by tracheal spirals and lung parenchymal strips from normal and ovalbumin-sensitized guinea pigs was measured in vitro, after challenge with histamine, carbachol, leukotriene (LT) C4, LTD4, or a prostaglandin endoperoxide analog (U-44069). The responses and sensitivity of airway tissues to the above agonists were identical in normal and sensitized animals. Treatment of tracheal spirals with indomethacin (8.5 μM), phenidone (185 μM), and nordihydroguaiaretic acid (NDGA: 30 μM) reduced resting tension (tone) equally in both normal and sensitized trachea, but did not affect lung parenchymal strips from either group. The responses of tracheal spirals from normal and sensitized animals to low concentrations of histamine, carbachol, LTC4, and LTD4 were reduced or abolished by treatment with the above inhibitors. Responses to higher concentrations of the same agonists were significantly enhanced. In contrast, treatment of normal and sensitized trachea with indomethacin (2.8 and 8.5 μM) did not abolish or reduce the effects of low concentrations of U-44069. However, an enhancement of the effect of high concentrations occurred only on normal tracheal spirals, even though the control tissues from each group responded identically with U-44069 in the absence of any inhibitor. Parenchymal strips increased in sensitivity to histamine, but not carbachol, as a result of time, vehicle, or prior exposure to the drug. Inhibitor treatment did not affect sensitivity or responsiveness of parenchyma to histamine, carbachol, and U-44069, but the contractile activity of LTD4 on both normal and sensitized lung parenchymal strips was reduced by indomethacin, NDGA, and phenidone. We conclude that ovalbumin sensitization does not induce hyperreactivity of guinea pig airways.
Theoretical analysis of adenosine release from cardiac tissue as influenced by transport inhibitors
Authors: Wiener H. , Schützenberger W. G. , Tuisl E. , Kolassa N.
Published: April 2011

The release of adenosine from cardiac tissue was simulated by use of a model equation which consists of a saturable transfer term for both unidirectional influx and efflux, representing a symmetrical facilitated diffusion mechanism. This proposed model can account for positive and negative changes in adenosine release from cardiac tissue brought about by competitive transport inhibitors.
FMRFamide effects on spontaneous and induced contractions of the anterior gizzard in Aplysia
Authors: Austin Tom , Weiss Sam , Lukowiak Ken
Published: April 2011

The effects of FMRFamide (Phe-Met-Arg-Phe-NH2), YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2), and Met-enkephalin (Tyr-Gly-Gly-Phe-Met) on the isolated Aplysia anterior gizzard were examined. (i) FMRFamide inhibits spontaneous gut activity. While YGG-FMRFamide also inhibits spontaneous activity it is less potent than FMRFamide. Met-enkephalin does not affect spontaneous gut activity. (ii) FMRFamide inhibits the excitatory response of acetylcholine on both the anterior gizzard of Aplysia and the isolated stomach region of Navanax. (iii) Neither FMRFamide, YGG-FMRFamide, Met-enkephalin, nor acetylcholine stimulated the activity of adenylate cyclase in the Aplysia anterior gizzard.
Role of vasopressin in the control of arterial pressure
Authors: McNeill J. Robert
Published: April 2011

Elevations in the circulating levels of vasopressin within the physiological range (less than 30 fmol ∙ mL−1) in conscious animals cause vasoconstriction of resistance vessels, the most profound effect occurring in the muscle, skin, and intestinal vascular beds. In the organism with normal baroreceptor function, the vasoconstriction is not expressed as an increase in arterial pressure because of a corresponding fall in cardiac output associated with enhanced cardiovascular reflex activity. When compensatory reflex mechanisms are impaired (baroreceptor-denervated dogs, patients with autonomic insufficiency, hypertensive rats), the vasoconstrictor activity of vasopressin is exposed and is reflected as an increase in arterial pressure. Inactivation of the vasopressin system alone by hypophysectomy or by administration of antagonists of the pressor activity of vasopressin is often accompanied by compensatory activation of the rennin–angiotensin system. Thus, under certain conditions, the vasopressin system and the renin–angiotensin system operate as reciprocal or redundant mechanisms in the control of resistance vessels and of arterial pressure. In two rat models of hypertension (spontaneously hypertensive rats and DOC-salt hypertensive rats) plasma levels of vasopressin are elevated, inactivation of the vasopressin system lowers arterial pressure, and pressor responsiveness to the peptide is enhanced. The enhanced pressor responsiveness appears related in part to impaired reflex activity. The mechanism of the impaired reflexes is unknown but in spontaneously hypertensive rats it might be related to a vasopressin deficit in the paraventricular nucleus and brain stem. The evidence is consistent with the possibility that vasopressin is one factor among many that may play a role in the maintenance of arterial pressure in the adult spontaneously hypertensive rat and in the development and maintenance of the hypertensive state in DOC-salt hypertensive rats.
Atrial natriuretic factor and urinary kallikrein in the rat: antagonistic factors?
Authors: Thibault Gaétan , Garcia Raul , Cantin Marc , Genest Jacques
Published: April 2011

The rat atrium contains a potent natriuretic factor which appears to inhibit the sodium reabsorption in the collecting tubules of the kidneys. We examined the effects of the injection of partially purified atrial natriuretic factor (ANF) and synthetic ANF (8-33) into rats with simultaneous infusions of dextrose or aprotinin. Aprotinin, an inhibitor of serine proteases, increases the natriuretic and diuretic effects of the atrial factor by 50%. Urinary kallikrein excretion is also slightly increased by ANF but is not affected by aprotinin. As a comparison, aprotinin has no effect on the diuretic or natriuretic responses of furosemide, although it inhibits by 50% the kallikrein excretion induced by furosemide. When ANF is incubated with purified rat urinary kallikrein, the natriuretic and diuretic effects are decreased by more than 50%. We conclude that glandular kallikrein or a similar serine protease may be involved in the catabolism of ANF.
Methyl parathion and fenvalerate toxicity in American kestrels: acute physiological responses and effects of cold
Authors: Rattner B. A. , Franson J. C.
Published: April 2011

Physiological and toxicological effects of p.o. methyl parathion (0.375–3.0 mg/kg) or fenvalerate (1000–4000 mg/kg) were examined over a 10-h period in American kestrels (Falco sparverius) maintained in thermoneutral (22 °C) and cold (−5 °C) environments. Methyl parathion was highly toxic (estimated median lethal dose of 3.08 mg/kg, 95% confidence limits of 2.29–4.14 mg/kg), producing dose-dependent inhibition of brain and plasma cholinesterase activity, hyperglycemia, and elevated plasma corticosterone concentration. Brain and plasma cholinesterase inhibition in excess of 50% was associated with transient but pronounced hypothermia 2 h after intubation, although the magnitude of this response was variable. Fenvalerate, at doses far exceeding those encountered in the environment, caused mild intoxication and elevated plasma alanine aminotransferase activity. Cold intensified methyl parathion toxicity, but did not affect that of fenvalerate. Thus, it would appear that organophosphorus insecticides pose far greater hazard than pyrethroids to raptorial birds.
Calcium and myocardial cell injury. An appraisal in the cardiomyopathic hamster
Authors: Jasmin Gaëtan , Proschek Libuse
Published: April 2011

The heart muscle is very compliant within a wide range of physiologic impulses. The adaptive energy of the myocardium depends, however, upon adequate oxygen supply and the functional state of the plasmalemma. These limitations have been well demonstrated in a number of experimental models with emphasis on the essential role of Ca2+ transmembrane movements for maintenance of heart functions and its viability. This postulate appeared quite important when we found that Ca2+ slow channel blockers could prevent necrotic changes in hamster hereditary cardiomyopathy. However, the effectiveness of β-adrenoagonists when given in low doses seems more difficult to interpret since these agonists can only promote Ca2+ transmembrane movements. We can only surmise that Ca2+ accumulation in cardiomyopathic hearts does not derive from a primary defect of the plasmalemma but rather from an exhausted hypokinetic state that favours Ca2+ accumulation with progressive deterioration of the structural proteins. It is thus inferred that Ca2+ mediates rather than initiates the degradation process which characterizes this inherited cardiomyopathy.
Tissue blood flow in control and cold-adapted hyperthyroid rats
Authors: Rothwell Nancy J. , Stock Michael J.
Published: April 2011

Chronic injections (once daily for 10–14 days) of triiodothyronine (T3) stimulated oxygen consumption by 50 and 15% in anaesthetized, control (24 °C), and cold-adapted (5 °C) rats, respectively, compared with euthyroid controls. Tissue blood flow, determined from the distribution of radioactive microspheres, was unaffected by T3 treatment in skeletal muscle, scrotum, brain, bone, skin, diaphragm, and brown adipose tissue (BAT) of rats housed at 24 °C, but was decreased in spleen (53% of control) and significantly increased in three white adipose tissue depots (average 267% increase) and liver (56%). Blood flow to epididymal fat and leg muscle of cold-adapted rats was increased by T3 treatment (100 and 138% increases, respectively), but other tissues were unaffected. Blood oxygen extraction and oxygen consumption in vivo by interscapular BAT was increased in hyperthyroid rats compared with euthyroid controls, but was reduced by T3 treatment in cold-adapted animals. These data show that BAT makes only a minor contribution (7%) to thyroid thermogenesis, but suggest that kidney, liver, gut, and particularly white adipose tissue may be involved.
The use of antimicrobial drugs in agriculture
Authors: Black W. D.
Published: April 2011

Antibacterial drugs have been used widely in animal production for treatment and prevention of disease and for growth promotion. Concern has been expressed about possible harm to humans, through the use of drugs, in the following ways: (1) increased microbial drug resistance; (2) drug residues in food; (3) allergic reactions and sensitization to antimicrobials; and (4) drug toxicity. Research has shown that microbial resistance in people can develop from drugs used in animals. Farmers, butchers, etc., have been shown to have an increased incidence of drug-resistant organisms. Resistance to antibiotics can develop in two ways; genetic mutation and natural selection, and through R-factor plasmid transfer. Allergic reactions have been reported following the ingestion of penicillin-containing milk; however, residues in other foods have not caused allergic reactions. Sensitization of humans to antimicrobials through the consumption of drug residues in foods has never been documented. Evidence suggests that the residue levels in food are too low to cause sensitization. Drug toxicity, other than allergic reactions, appears not to result from residues of antimicrobial drugs in food. While it has been studied many times, monitoring programs have failed to find any evidence of a problem. This appears to reflect the low toxicity of these agents and the small amounts obtained in the food, however, it could also reflect failure of the monitoring systems.
The agricultural use of municipal sewage
Authors: Hamilton Donald L. , Brockman Ronald P. , Knipfel J. E.
Published: April 2011

The reuse of municipal sewage for agricultural purposes is becoming more prevalent. The literature concerning the impact of this practice is reviewed. It is readily apparent that agricultural reuse of municipal sewage is prefereable to other common methods of disposal both from the point of view of ecological influence and economical waste utilization. There is a need to establish guidelines for the agricultural use of municipal sewage which will serve the variable conditions found in Canada and meet the public health concerns associated with an extensive agricultural use.
Effects of prostaglandin E2 on salicylate-induced damage to the rat gastric mucosa: cytoprotection is not associated with preservation of the gastric mucosal barrier
Authors: Morris Gerald P. , Wallace John L. , Harding Patricia L.
Published: April 2011

The effects of pretreatment with prostaglandin E2 (PGE2) on salicylate-induced gastric damage in the rat were studied with a gastric chamber model. Transmural potential difference (PD) and net potassium ion (K+) efflux were monitored as indices of gastric mucosal barrier integrity. Topical application of 20 mM salicylate for 10 min produced an abrupt drop in PD, an increase in net K+ flux, and the formation of hemorrhagic erosions covering approximately 24% of the glandular mucosa. Prior topical application of PGE2 at doses of 25, 75, and 300 μg/kg significantly reduced the extent of hemorrhagic erosions. However, PG pretreatment did not produce a reduction in the effects of topical salicylate on either PD or net K+ efflux. Rather, the drop in PD was initially accelerated and the net K+ efflux was increased by PGE2 pretreatment. Subsequently, in PGE2-pretreated mucosae, both parameters showed more rapid recovery toward control values. These results suggest that the mechanism of "cytoprotection" by PGE2 against salicylate-induced gastric damage is not a consequence of preservation of the gastric mucosal barrier.
Facilitated diffusion of monosaccharides in smooth muscle of rat vas deferens in vitro
Authors: Elbrink J.
Published: April 2011

The suitability of rat vas deferens for investigating sugar transport in smooth muscle was determined in vitro, with the nonmetabolized glucose analog 3-O-methyl-D-glucose as test sugar. Vas deferens smooth muscle contains a facilitated diffusion system for monosaccharides, as shown by saturation of the transport sites and by competition between 3-O-methyl-D-glucose and D-glucose. The activity of the facilitated diffusion system could be enhanced by hyperosmolarity and by contractile activity, but frequency dependency could not be established. A high concentration of insulin (100 mU/mL) was required to stimulate sugar transport. As smooth muscle is not a primary tissue for the storage of energy reserves, it does not require large numbers of insulin receptors.
Effects of isoproterenol and forskolin on tension, cyclic AMP levels, and cyclic AMP dependent protein kinase activity in bovine coronary artery
Authors: Vegesna Raju V. K. , Diamond Jack
Published: April 2011

The effects of isoproterenol and forskolin on tension, cyclic AMP levels, and cyclic AMP dependent protein kinase activity were compared in helical strips of bovine coronary artery. Elevation of cyclic AMP and activation of the protein kinase appeared to be well correlated with relaxation of potassium-contracted arteries by isoproterenol. Forskolin, at 1 μM or higher concentrations, also markedly elevated cyclic AMP levels, activated the kinase, and relaxed the arteries. However, a lower concentration of forskolin (0.1 μM) caused significant increases in both cyclic AMP levels and cyclic AMP dependent protein kinase activity, but did not relax the muscles. Relaxation caused by isoproterenol was accompanied by an apparent translocation of cyclic AMP dependent protein kinase activity from the soluble to the particulate fraction in these preparations. A similar shift in the distribution of the kinase was caused by various concentrations of forskolin, irrespective of whether the arteries were relaxed or not. In contrast to previous results in other tissues, low concentrations of forskolin (≤ 1 μM), which themselves markedly elevated cyclic AMP levels in the arteries, did not potentiate the effects of isoproterenol on cyclic AMP levels or tension in these preparations. These results suggest that either cyclic AMP is not solely responsible for the relaxation caused by these agents, or some form of functional compartmentalization of cyclic AMP and cyclic AMP dependent protein kinase exists in this tissue.
Intestinal absorption of zinc: competitive interactions with iron, cobalt, and copper in mice with sex-linked anemia (sla)
Authors: Flanagan P. R. , Haist J. , MacKenzie I. , Valberg L. S.
Published: April 2011

Duodenal uptake and transfer of 59Fe and 65Zn and absorptive interactions between iron, zinc, cobalt, and copper were studied in sla mice and in genetically normal Swiss albino control mice. Genetically normal mice with a high iron-absorbing capacity, induced by being fed an iron-deficient diet, showed greater uptake and transfer of 65Zn in duodenum but not ileum, compared with mice with a low iron-absorbing capacity. 59Fe transfer from the duodenal mucosa to the body was lower in sla mice compared with controls and bleeding stimulated the capacity to absorb 59Fe less in sla mice relative to normal controls. In contrast, 65Zn transfer in sla was no different from controls and was not stimulated by bleeding in sla or in control mice. Iron or cobalt in a 10-fold molar excess predominantly lowered 65Zn transfer in both sla and controls, but in a study of the effect of zinc on iron transport only the uptake of 59Fe in sla mice was lowered by excess zinc in the perfusate. The effect of added copper on 65Zn transport was paradoxical; in both sla and control mice copper markedly increased 65Zn uptake relative to perfusates containing 65Zn alone, but transfer in normal mice was lowered whereas it was increased in sla animals. The interaction between zinc and iron does not appear to take place at the site of the genetic defect in sla mice. The lesion in iron transport in these mice is likely due to defective binding and transfer sites in the basolateral membrane; these sites are apparently exclusive for iron and not shared by zinc.
Influence of hypercapnia and (or) hypoxemia and metabolic acidosis on sulfamethazine kinetics in the conscious rabbit
Authors: Souich Patrick du , Courteau Hélène
Published: April 2011

The aim of the present study was to determine whether acute changes in blood gases and pH alter sulfamethazine (SMZ) kinetics. Groups of conscious rabbits were exposed for 270 min either to air or to a high CO2 and (or) low O2 atmosphere to produce hypercapnia, hypoxemia, or both. Another group of rabbits received 47 mL/kg of 0.3 M HCl by gavage tube to induce metabolic acidosis. Once the blood gases were stabilized, the rabbits received 20 mg/kg SMZ i.v. Multiple blood samples were drawn for 180 min to assess SMZ kinetic parameters, SMZ protein binding, and blood gases. Fifteen minutes after the administration of SMZ, a suboccipital puncture was performed to determine the concentration of SMZ in the cerebrospinal fluid (CSF). Urine was collected for the first 180 min through a sterile catheter and for the next 21 h in a metabolic cage. Hypercapnia alone did not significantly influence SMZ kinetics. Hypoxemia, hypoxemia combined with hypercapnia, and metabolic acidosis increased the SMZ apparent volume of distribution (V) and total body clearance (CL). This increase in the SMZ V correlated positively (p < 0.01) to the ratio of SMZ concentration in CSF to SMZ concentration in plasma. The increase in SMZ CL was mainly due to an increase in nonrenal clearance, although a slight increase in SMZ renal clearance was also observed. Several factors may be related to these kinetic changes: (i) SMZ plasma protein binding decreased under these experimental conditions as a result of a decrease in the apparent intrinsic association constant; (ii) in addition, SMZ nonionized fraction may have increased by 42% in hypercapnia combined with hypoxemia and metabolic acidosis; (iii) theoretically, changes in blood flow distribution may have also contributed. It was concluded that the acute modification of blood gases and pH do influence SMZ kinetics, hypoxemia being the factor most responsible for kinetic changes.
Analysis of adrenergic responses in the mesenteric vascular bed of the cat; evidence that vascular beta2-adrenoceptors are innervated
Authors: Armstead William M. , Lippton Howard L. , Hyman Albert L. , Kadowitz Philip J.
Published: April 2011

Responses to sympathetic nerve stimulation and pressor hormones were investigated in the feline mesenteric vascular bed under conditions of controlled blood flow. Sympathetic nerve stimulation and norepinephrine produced frequency- and dose-dependent increases in mesenteric vascular resistance. However, when alpha-receptors were blocked with the non-equilibrium alpha-receptor antagonist, phenoxybenzamine, nerve stimulation and norepinephrine produced frequency- and dose-dependent decreases in mesenteric vascular resistance. These reductions in mesenteric vascular resistance were unchanged after indomethacin or atropine, whereas propranolol converted the mesenteric vasodilator responses to small vasoconstrictor responses. In these studies, responses to a variety of vasoconstrictor agents were enhanced after administration of propranolol. Sotalol, a nonselective beta blocker with little membrane stabilizing activity, also enhanced vasoconstrictor responses. The present data suggest that both alpha- and beta-adrenergic receptors are innervated in the feline mesenteric vascular bed, and that vasodilator responses to norepinephrine and sympathetic nerve stimulation are independent of activation of muscarinic receptors or formation of products in the cyclooxygenase pathway. These data also demonstrate that there is a nonspecific potentiation of intestinal vasoconstrictor responses after beta-adrenergic receptor blockade that is independent of a membrane-stabilizing or receptor-mediated mechanism.
Pancreatic growth and enzyme profiles in weanling rats with normophagic hypothalamic obesity
Authors: Bernardis Lee L. , Lee Ping C. , Brooks Stephen , Lebenthal Emanuel
Published: April 2011

Weanling male rats with ventromedial hypothalamic lesions (VMNL rats) and sham-operated controls were killed 1, 2, 4, and 5 weeks postoperatively. The VMNL rats developed normophagic hypothalamic obesity in the presence of normal body weight and reduced linear growth. In both VMNL and control rats, pancreatic weight and protein content increased with time but were lower in the lesioned animals. Pancreatic DNA content was arrested in VMNL rats and remained so during the remainder of the experiment. The only significant enzyme changes (trypsinogen, amylase, and lipase) were evident in higher trypsinogen concentration in VMNL rats during 2 and 4 weeks after lesion production. In view of previous data on both hypophysectomized and VMNL rats and the known role of the ventromedial hypothalamic nucleus in neuroendocrine and neuroautonomic function, it is speculated that the changes observed here are in part due to disruption of neuroendocrine and in part due to disturbance of neuroautonomic control systems.
Effect of phentolamine on the insulin, glucagon, and glucose responses to exercise in adrenal-denervated sheep
Authors: Brockman Ronald P.
Published: April 2011

Hyperglycemia and increased hepatic glucose output are characteristic responses to exercise in sheep. They appear to be due in part to α-adrenergic stimulation. To delineate the contributions of sympathetic innervation and adrenal catecholamines to the hormonal and metabolic responses to exercise, adrenal-denervated sheep were exercised with and without α-blockade (phentolamine treatment). Alpha blockade exaggerated the hyperinsulinemia during exercise (increment of 61 ± 8 vs. 34 ± 7 μU/mL for the control). This was associated with a reduction in glucose appearance (increments of 63 ± 8 vs. 236 ± 23 μmol/min, respectively). The metabolic clearance rates were not altered by α-blockade. It appears that both the adrenal catecholamines and adrenergic innervation to the pancreas contribute to the prevention of a rise in insulin concentrations during exercise in sheep. While this may not be essential for glucose appearance to rise during exercise, it appears necessary for an optimal response.
A review of changes in vascular smooth muscle functions in hypertension: isolated tissue versus in vivo studies
Authors: Triggle C. R. , Laher I.
Published: April 2011

The role of altered vascular smooth muscle function in the etiology of essential hypertension has been extensively studied by a number of investigators. The results obtained from in vivo studies do not always correlate with results from in vitro studies and it is not always apparent whether the results reflect differences related to hypertension or to the genetic background of the animal model. In vitro and perfused vascular bed studies in our laboratory have utilized the spontaneously hypertensive rat (SHR), the normotensive Wistar Kyoto rat (WKY), genetically related crossbred rats (F1, F2, and BC1), and also Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The role of altered smooth muscle function in relation to the development of the elevated blood pressure (BP) of the SHR or DS rat was studied and emphasis was placed on determining the role of altered neuronal uptake1 (U1) in hypertensives in masking elevated postsynaptic sensitivity to noradrenaline. In addition, the relationship between postsynaptic sensitivity to cations and BP was assessed. Such studies have indicated that alterations in postsynaptic sensitivity, U1 activity, and sensitivity to cations are not entirely consistent with the etiology of hypertension in the SHR and DS rat but may simply reflect genetic strain differences between the hypertensive and normotensive animals.
Primary versus secondary events in hypertension
Authors: Hamet Pavel , Tremblay Johanne , Pang Stephen C. , Walter Susan V. , Wen Yuen-I
Published: April 2011

Functional modifications, such as a reduction in hormonal response, which occur in the cardiovascular system in hypertension, are reflected at the cellular level by anomalies in cyclic nucleotide and other messenger systems. To distinguish between primary and adaptive abnormalities, we pursued three research strategies. (i) Investigations on various models of hypertension. To be considered a primary defect, an abnormality should also be present in other genetically hypertensive models. Indeed, we have confirmed the occurrence of cellular hyperplasia in the heart of spontaneously hypertensive rats (SHR) as well as in spontaneously hypertensive mice (SHM). An increase of calmodulin levels in the heart and kidney is also observed in both the SHR and SHM. (ii) Studies on the evolution of hypertension with age. In humans, a decrease of cAMP levels in response to β-adrenergic stimulation in older patients is contrasted with an excess in younger subjects. In the SHR, protein kinase activity of the heart is lower in the prehypertensive stages, whereas this defect appears much later in the aorta, (iii) Experiments on anomalies in newborns and cultured cells. The heart and kidney in the SHR exhibit significant hyperplasia at birth, and an abnormal growth continues in tissue culture. We hope that these strategies will eventually help to provide biochemical and functional markers for genetic analysis of factors which may be involved in the pathogenesis of hypertension.
The role of aortic chemoreceptors during severe CO hypoxia
Authors: King C. E. , Cain S. M. , Chapler C. K.
Published: April 2011

The importance of aortic chemoreceptors in the circulatory responses to severe carbon monoxide (CO) hypoxia was studied in anesthetized dogs. The aortic chemoreceptors were surgically denervated in eight dogs prior to the induction of CO hypoxia, with nine other dogs serving as intact controls. Values for both whole body and hindlimb blood flow, vascular resistance, and O2 uptake were determined prior to and at 30 min of CO hypoxia in the two groups. Arterial O2 content was reduced 65% using an in situ dialysis method to produce CO hypoxia. At 30 min of hypoxia, cardiac output increased but limb blood flow remained at prehypoxic levels in both groups. This indicated that aortic chemoreceptor input was not necessary for the increase in cardiac output during severe CO hypoxia, nor for the diversion of this increased flow to nonmuscle tissues. Limb O2 uptake decreased during CO hypoxia in the aortic-denervated group but remained at prehypoxic levels in the intact group. The lower resting values for limb blood flow in the aortic-denervated animals required a greater level of O2 extraction to maintain resting O2 uptake. When CO hypoxia was superimposed upon this compensation, an O2 supply limitation occurred because the limb failed to vasodilate even as maximal levels for O2 extraction were approached.
Transient inhibition of the muscarinic actions of carbachol during reactivation of the electrogenic sodium pump in guinea pig taenia caeci smooth muscle
Authors: Török Tamás L. , Vizi Sylvester E. , Magyar Kálmán
Published: April 2011

In guinea pig taenia caeci smooth muscle the muscarinic receptor stimulant carbachol evoked depolarization and contraction, which was followed by hyperpolarization and relaxation on its removal. Both the hyperpolarization and relaxation were inhibited by removal of K+ from the external medium. During Na+-pump blockade (K+-free solution) the depolarizing and contracting actions of carbachol decreased. When the Na+ pump was switched on again by readmission of 5.9 mmol/L K+ to K+-depleted and Na+-enriched preparations, electrogenic hyperpolarization and relaxation developed. During this period carbachol failed to produce depolarization and contraction.
Tension–velocity relationships in hypertensive mesenteric resistance arteries
Authors: Packer C. S. , Stephens N. L.
Published: April 2011

Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the tension–velocity (T–V) relationship in hypertensive resistance arterial smooth muscle. Increased narrowing in such arteries would result in increased resistance. The objectives of this investigation were to determine whether there is (i) increased narrowing capacity (−ΔC/Co where C stands for arterial internal circumference and Co is the optimal arterial internal circumference for maximum tension development); (ii) an increased maximum velocity of isobaric narrowing (Vmax) measured in Co per second; (iii) an increased wall thickness (h); and (iv) an increased active stress development (Tmax) in the spontaneously hypertensive rat (SHR; n = 5) compared with the normotensive Wistar Kyoto (WKY; n = 5) and MK-421 (an angiotensin I converting enzyme inhibitor) treated spontaneously hypertensive rat (MK-421 trt. SHR; n = 5) mesenteric resistance (diameter, < 300 μm) arteries. Analysis of the data for arteries constricting isobarically against a range of pressures revealed that (a) the SHR–ΔC/Co values at pressures ranging from 20 to 120 mmHg (1 mmHg = 133.322 Pa) showed significantly increased narrowing compared with the MK-421 trt. SHR and WKY–ΔC/Co values in this same pressure range (p < 0.01), and (b) the SHR derived Vmax of 0.83 ± 0.08 Co/s was significantly faster than either the MK-421 trt. SHR or WKY Vmax of 0.34 ± 0.06 and 0.28 ± 0.08 Co/s, respectively (p < 0.01); (c) the SHR mean h of 31 ± 3 μm was significantly thicker than either the MK-421 trt. SHR or WKY arteries of 22 ± 2 and 19.5 ± 0.5μm, respectively (p < 0.05); (d) the SHR, MK-421 trt. SHR, and WKY arteries showed no differences in Tmax which were 1016 ± 135, 897 ± 221, and 1077 ± 43 g/cm2, respectively (p > 0.05). This study provides evidence that while the hypertensive resistance arterial segments are not able to produce more tension than normotensive arterial smooth muscle, they are able to narrow faster and narrow more. The latter would result in increased resistance and could result in increased blood pressure.
A method to express complex curves concisely and with high fidelity
Authors: Bessette France , Seufert Wolf D.
Published: April 2011

Piecewise spline interpolation between judiciously selected points on a curve reproduces it with great precision. A number of points much smaller than in current digitization techniques is needed and their positions fully characterize a curve. We present the rules to select the nodal points and we demonstrate that their positions are very sensitive to changes in wave form. They can therefore be used to identify a curve in parts or in its entirety, to the extent to provide its mathematical definition.
α1-Adrenergic receptor involvement in norepinephrine–ethanol inhibition of rat brain Na+-K+ ATPase and in ethanol tolerance
Authors: Rangaraj N. , Kalant H. , Beaugé F.
Published: April 2011

Norepinephrine (NE) sensitization of rat brain Na+–K+ ATPase to ethanol (EtOH) inhibition appears to be mediated by α1-adrenoreceptors, since it was reversed by prazosin and WB-4101 (α1-receptor antagonists) in a concentration-dependent manner, but not by yohimbine and piperoxan (α2-receptor antagonists). In addition, clonidine (α2-agonist) and methoxamine (central receptor type uncertain) produced very little sensitization. Chronic EtOH administration to rats for 3 weeks produced tolerance to the hypothermic effect of test doses of EtOH (3 g/kg, i.p.) and a decreased inhibitory effect of NE + EtOH on the enzyme in vitro. This inhibition was still prevented by prazosin and WB-4101. However, the binding of tritiated WB-4101 and prazosin to brain membrane preparations from control and EtOH-tolerant rats revealed that the maximum number of binding sites (Bmax) and the dissociation constant (KD) of α1-adrenoreceptors were decreased after tolerance development. These changes in numbers and binding properties of α1-adrenoreceptors probably account for the decreased NE sensitization of the ATPase to EtOH inhibition in preparations from EtOH-tolerant rats.
Comparative effects of vasodilator drugs on flow distribution and venous return
Authors: Ogilvie R. I.
Published: April 2011

Systemic vascular effects of hydralazine, prazosin, captopril, and nifedipine were studied in 115 anesthetized dogs. Blood flow [Formula: see text] and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant [Formula: see text] showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. At three dose levels producing comparable reductions in systemic arterial pressure (30–40% at the highest dose), these drugs had different effects on flow distribution and venous return. Hydralazine and prazosin had parallel and balanced effects on arterial resistance of the two vascular compartments, and flow distribution was unaltered. Captopril preferentially reduced arterial resistance of the compartment with a slow time constant for venous return (−26 ± 6%, −30 ± 6%, −50 ± 5% at 0.02, 0.10, and 0.50 mg∙kg−1∙h−1, respectively; [Formula: see text]) without altering arterial resistance of the fast time-constant compartment. Blood flow to the slow time-constant compartment was increased 43 ± 14% at the highest dose, and central blood volume was reduced 108 ± 15 mL. In contrast, nifedipine had a balanced effect on arterial resistance with the lowest dose (0.025 mg/kg) but caused a preferential reduction in arterial resistance of the fast time-constant compartment at higher doses (−38 ± 4% and −55 ± 2% at 0.05 and 0.10 mg/kg, respectively). Blood flow to the slow time-constant compartment was reduced 36 ± 5% at the highest dose of nifedipine, and central blood volume was increased 66 ± 12 mL. Total systemic venous compliance was unaltered or slightly reduced by each of the four drugs. These results add further evidence to the hypothesis that peripheral blood flow distribution is a major determinant of venous return to the heart.
Renal brush border membrane phosphorylation: influence of pH, cAMP and ATP concentrations, parathyroid hormone status, and dietary phosphate
Authors: Brunette Michèle G. , Allard Serge
Published: April 2011

It is known that parathyroidectomy, administration of parathyroid hormone (PTH), and dietary phosphate depletion or excess result in variations in phosphaturia and in phosphate transport through brush border membrane vesicles isolated from the kidneys of various animals. Parathyroid hormone has been shown to ultimately phosphorylate some brush border membrane proteins and it has been postulated that the resulting phosphaturia is related to this phosphorylation. However, it is not known whether the regulation of phosphate transport by the diet is affected through similar pathways. Our experiments were designed to study the phosphorylation of brush border membrane with [γ-32P]ATP using the intrinsic protein kinase of the membranes. Five groups of rats were used: normal, phosphate loaded, phosphate depleted, and thyroparathyroidectomized and acutely loaded with parathyroid hormone. In each series of animals, the proteins whose phosphorylation was cAMP dependent were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and their phosphorylation with various concentrations of ATP, in the presence or absence of cAMP in the incubation medium, was quantified. In the normal rat, 17 proteins were phosphorylated, the phosphorylation of two of them (Mr, 71 000 and 84 000) being cAMP dependent. Maximal response to cAMP for these two proteins was obtained with 10 μM cAMP. The peaks of phosphorylation were observed at pH 7 for protein 71 000 and pH 10 for protein 84 000. When brush border membranes from normal rats were incubated with 10–100 μM ATP, cAMP-dependent phosphorylation increased to reach a maximal phosphorylation of 4.44 ± 0.90 pmol/mg protein for protein 71 000 and 1.32 ± 0.15 pmol/mg protein for protein 84 000. The Km values were 51.1 ± 6.4 and 23.2 ± 0.4 μM, respectively. With 10 μM ATP, cAMP-dependent phosphorylation of protein 71 000 was not significantly influenced by the PTH status nor the diet. In contrast, both the parathyroid hormone status and the diet affected the cAMP-dependent phosphorylation of protein 84 000 by changing the Km values for ATP: 14.7 ± 1.7 and 14.6 ± 2.9 μM ATP in thyroparathyroidectomized and phosphate-depleted animals; 31.3 ± 4.4 and 29.8 ± 3.5 μM ATP in parathyroid hormone and phosphate-loaded animals, respectively. It is concluded that (i) the rat brush border membrane contains two main proteins whose phosphorylation is cAMP dependent, (ii) both the PTH status and diet similarly affect the protein kinase responsible for the phosphorylation of protein 84 000 by changing its affinity for ATP, (iii) unless the concentration of ATP available for this enzyme approximates the Km values observed by us and others (50–100 μM), these changes in affinity for ATP have no impact on final membrane phosphorylation.
Autoradiographic localization of binding sites for atrial natriuretic factor
Authors: Schroeder H. P. von , Nishimura E. , McIntosh C. H. S. , Buchan A. M. J. , Wilson N. , Ledsome J. R.
Published: April 2011

The distribution of atrial natriuretic factor (ANF) binding sites in Wistar rat tissues, as well as tissues from other species was studied. Using autoradiography of slide mounted tissue sections incubated with 125I-labelled ANF, high densities of binding sites were found in the renal glomeruli and papilla, aortic smooth muscle, iliac vein, choroid plexus, anterior pituitary, lung, and adrenal zona glomerulosa. Results from renal, aortic, adrenal, and lung tissues from spontaneously hypertensive rats did not differ from those of Wistar rats. Binding sites were also observed in guinea pig glomeruli, renal medulla, and aorta as well as in the rabbit aorta.
Influence of dietary lipids on arrhythmias and infarction after coronary artery ligation in rats
Authors: McLennan P. L. , Abeywardena M. Y. , Charnock J. S.
Published: April 2011

Coronary artery ligation (CAL) was used to produce an in vivo model of cardiac arrhythmias and myocardial infarction using anaesthetized male Hooded Wistar rats which had been fed for 6–7 or 18–20 months on either a standard reference diet alone or supplemented (12% w/w) with sunflower seed oil (linoleic acid rich) or sheep kidney fat (linoleic acid poor). The number of ventricular extra beats and duration of tachycardia or fibrillation in the 30-min postligation was increased in sheep kidney fat-fed rats. Infarct size 4 h postCAL was reduced in sunflower seed oil-fed rats. Arrhythmias, infarct size, and dietary-induced differences were increased with age. The diets employed produce changes in myocardial membrane phospholipids which could result in altered prostaglandin production. These results show that in the rat (as in man), age and dietary saturated fat are risk factors for sudden cardiac death and myocardial infarction and suggest that the rat is a useful model for the investigation of dietary interventions in heart disease.
Central vasopressin in the modulation of catecholamine release in conscious rats
Authors: King Kathryn A. , Mackie Gordon , Pang Catherine C. Y. , Wall Richard A.
Published: April 2011

Neurons containing arginine vasopressin (AVP) have been shown to project from the paraventricular nucleus of the hypothalamus to the nucleus tractus solitarius (NTS) in the medulla. We investigated whether AVP acts in brain stem regions to influence sympathoadrenal outflow. Cannulae were implanted into the fourth ventricle of rats 7 days prior to the experiment. The effects of intracerebroventricular (icv) injections of AVP, the vehicle, and AVP antagonist, d(CH2)5Tyr(Me)AVP, on mean arterial pressure (MAP) and plasma noradrenaline (NA) and adrenaline (A) levels were determined in conscious unrestrained rats. Injections of AVP (icv, 23 and 73 ng/kg) but not the vehicle increased MAP and plasma NA and A levels. In contrast, iv injection of AVP increased MAP but decreased plasma concentrations of A and NA. The pressor response to icv injection of AVP was abolished by prior icv injection of AVP antagonist. Injection of AVP antagonist (icv, 0.5 and 1.5 μg/kg) had no effect on MAP or plasma NA or A levels. These results show that centrally injected AVP activates sympathoadrenal outflow, possibly via an inhibition of baroreceptor reflexes. Since centrally administered AVP antagonist did not influence MAP or plasma NA or A levels, it appears that endogenously released AVP does not have a tonic influence on central cardiovascular reflex system in conscious, unrestrained rats.
Substrate utilization by the distal nephron in dogs with chronic metabolic acidosis: studies with ethacrynic acid
Authors: Halperin Mitchell L. , Chen Ching B.
Published: April 2011

Glutamine and lactate oxidations provide the bulk of ATP required for sodium reabsorption in the dog kidney during chronic metabolic acidosis. Indirect evidence has suggested that glutamine is oxidized in the proximal convoluted tubule; if this is true, lactate should be the major fuel of the more distal nephron sites. The purpose of these experiments was to determine which substrates were metabolized by the acidotic dog kidney when a significant proportion of sodium chloride reabsorption was inhibited in the thick ascending limb of the loop of Henle. Ethacrynic acid, a loop diuretic, caused the fractional excretion of sodium to increase from 1 to 34%. The glomerular filtration rate declined somewhat, but there was no significant change in the renal blood flow rate. Renal oxygen consumption declined in conjunction with the natriuresis. However, when the data were examined at a constant filtered load of sodium (a constant rate of ATP turnover), there was no reduction in glutamine uptake or glutamine conversion to ATP in the presence of this natriuretic agent. The major change observed concerned lactate metabolism, in the presence of ethacrynic acid, there was no longer a significant rate of lactate extraction. These data are best explained by assuming that glutamine is the fuel of the proximal convoluted tubule of the acidotic dog kidney, whereas lactate oxidation occurs principally in the nephron sites where sodium reabsorption was inhibited by ethacrynic acid.
Transplacental 45Ca and 32P flux in the guinea pig: effect of maternal hypercalcaemia and hypocalcaemia
Authors: Derewlany L. O. , Radde I. C.
Published: April 2011

Transplacental 45Ca and 32P flux was measured across the in situ perfused guinea-pig placenta under conditions of acute maternal hypocalcaemia and hypercalcaemia. Maternal hypercalcaemia induced acutely by calcium gluconate infusion caused an increase in maternal-to-fetal 45Ca flux which was proportional to the increase in maternal plasma ionized calcium concentration. Acute maternal hypocalcaemia was induced by EGTA infusion and resulted in a decrease in maternal plasma ionized calcium concentration proportional to a corresponding decrease in transplacental 45Ca transfer. A bolus of calcium gluconate caused a transient decrease in 32P flux, whereas EGTA administration was without significant effect on transplacental 32P transfer. Calcium transport across the placenta is not saturated under conditions of maternal normocalcaemia and may be altered according to acute changes in maternal plasma calcium concentration. Thus, control of maternal-to-fetal calcium transfer does not appear to be at the placental level. This suggests that fetal calcium homeostasis may be regulated by the fetus itself.
Involvement of the ventrolateral medulla in the mediation of pressor responses of the rat to afferent vagal stimulation
Authors: Kubo T.
Published: April 2011

Electrical stimulation of afferent vagal fibres evoked a pressor response in rats after transection of the spinal cord. The pressor response was accounted for by an increased release of vasopressin because it was abolished by the intravenous injection of a vasopressin antagonist. Bilateral electrolytic lesions at the sites of the caudal ventrolateral medulla markedly reduced the pressor response to afferent vagal stimulation but not that to carotid occlusion. It is concluded that the area of the caudal ventrolateral medulla is involved in mediation of the vasopressin-induced pressor response to afferent vagal stimulation.
Studies on a modulatory role for adenosine in antigen and arachidonic acid induced contractions of guinea pig airways
Authors: Burka John F.
Published: April 2011

The modulatory effects of adenosine and selected derivatives were examined on antigen and arachidonic acid (AA) induced contractions of indomethacin-treated tracheal spirals and lung parenchymal strips from actively sensitized guinea pigs. Adenosine (up to 2 × 10−4 M) had no effect on antigen-induced contractions, but inhibited AA-induced contractions by 30–40% if added 30 min prior to challenge. The weak effect of adenosine suggests that endogenous adenosine may only have a limited modulatory role in allergic bronchospasm. 2-Chloroadenosine (10−6–10−4 M) dose-dependently inhibited antigen- and AA-induced contractions of trachea, but was considerably less effective on parenchyma. The substituted adenosine derivatives, R-phenylisopropyladenosine (R-PIA) and 5′-(N-ethylcarboxamido)-adenosine (NECA), and the adenosine transport inhibitor, 6-[p-nitrobenzyl)thio]-9-β-D-ribofuranosyl purine, were also active as modulators, but their activity was relatively weak and varied with the stimulus and the tissue. An order of potency for R-PIA, NECA, and 2-chloroadenosine could not be determined and 8-phenyltheophylline (10−5 M) was not an effective inhibitor of the effects of adenosine or the adenosine derivatives. This suggests that adenosine and its derivatives may modulate cells through mechanisms other than activation of conventional A1 and A2 receptors. A lack of specificity for the adenosine derivatives must also be considered.