bluuebunny/crossref_metadata_2025 huggingface dataset:
Some observations on the determination of extracellular fluid volume of jejunal tissue using [3H]inulin and [14C]inulin
Authors: Dinda P. K. , Beck I. T. , Beck M.
Published: April 2011

The objective of the present study was to examine the nature of equilibration of [3H]-inulin and [14C]inulin in the jejunal tissue in vitro. Rings of everted hamster jejunum were incubated at 37 °C in Krebs Ringer bicarbonate solution containing 10 mM glucose, tracer amounts of [14C]inulin, and tracer amounts of [3H]inulin from one of the two lots (lot X and lot Y) tested. The incubations were carried out for 5, 10, 20, 30, 45, or 60 min. One lot of [3H]inulin (lot X) provided an estimate of the extracellular (EC) fluid volume which, at all periods of incubation, was comparable with that provided by the [14C]inulin. In contrast, the estimate of EC fluid volume obtained from the other lot of [3H]inulin (lot Y) was consistently higher than that obtained from the [14C]inulin and increased linearly with the period of incubation. Because, with [3H]inulin of lot Y, the calculated intracellular (IC) fluid volume decreased linearly with the period of incubation, and because this was not the case with the [14C]inulin or with the [3H]inulin of lot X, it would appear that [3H]inulin of lot Y failed to equilibrate within the tissue water, while the other lot of [3H]inulin (lot X), as well as [14C]inulin, did. Although the EC fluid volume obtained from [14C]inulin (as well as that from [3H]inulin of lot X) increased progressively, the rate of increase during the first 30 min was considerably higher than that during the last 30 min of incubation. The progressive increase in the [14C]inulin space, however, was accompanied by a corresponding increase in the total water content as well as in the calculated IC fluid content of the tissue. Since the IC fluid volume as percentage of total water content after 5 min of incubation was not significantly different from that after 60 min of incubation, it would appear that [14C]inulin equilibrates within the EC fluid after 5 min, and that the progressive increase in the calculated EC fluid volume is the result of a corresponding increase in the EC fluid (containing [14C]inulin) content of the tissue.
Digestibility and nutrient value of palmitoyl-L-lysine derivatives in weanling rats
Authors: Stephens Christian A. , Veen-Baigent Margaret J. , Paquet Alenka , Anderson G. Harvey
Published: April 2011

α-N,ε-N-Dipalmitoyl-L-lysine, α-N-monopalmitoyl-L-lysine, and ε-N-monopalmitoyl-L-lysine were compared with 18% casein and lysine HCl as sources of lysine in the diets of weanling rats. The lysine derivatives and lysine HCl were added to a basal diet containing 14.1% of an amino acid mixture with no lysine. Weight gain, food intake, plasma lysine, and urine and fecal lysine were determined. Animals fed the basal and lysine derivative diets lost weight over the 10-day study period. They had lower food intake, urine and plasma lysine content, and a higher fecal lysine content than animals fed the other diets. α-N-Monopalmitoyl-L-lysine was absorbed whereas the ε-N-monopalmitoyl-L-lysine and the α-N,ε-N-dipalmitoyl compounds were not.
Inhibition of hypoxic pulmonary vasoconstriction by dipyridamole is not platelet mediated
Authors: Mlczoch Johannes , Weir E. Kenneth , Grover Robert F.
Published: April 2011

Dipyridamole, which is known to alter platelet function, has also been shown to reduce hypoxic pulmonary vasoconstriction. This latter effect could result from dipyridamole either acting on a platelet-mediated system, or acting directly on pulmonary vascular smooth muscle. To investigate these two possibilities, normal dogs were compared with dogs rendered thrombocytopenic by a platelet antiserum. Compared with the hypoxic pressor response before drug treatment, the hypoxic response following dipyridamole was only 32% as great in the normal dogs and only 38% as great in the thrombocytopenic dogs. Thus, dipyridamole was no less effective in reducing the hypoxic pressor response in the virtual absence of platelets. This supports a direct effect of dipyridamole on pulmonary vascular smooth muscle, which could be mediated by an increase in adenosine levels.
Experimental aldosterone hypertension in the rat
Authors: Darke A. C. , Melnyk J. , Nair P. G. , Gaskell P.
Published: April 2011

We previously showed that hypertension induced in rats by administration of desoxycorti-costerone acetate and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension) was associated with an increased critical opening pressure (COP) of tail vessels and an increased arteriolar smooth muscle reactivity to intravenous infusion of angiotensin II or norepinephrine. In the present investigation hypertension was induced in rats by administration of aldosterone (5 μg/100 g per day) and replacement of drinking water with 1% NaCl solution (aldosterone–NaCl hypertension). The hypertension was associated with an increase in COP of tail vessels when measured both before and after ganglionic blockade, but the reactivity of the smooth muscle of these vessels to angiotensin II or to norepinephrine was not increased. Administration of aldosterone alone by intramuscular injection in sesame oil induced hypertension, whereas it was previously shown that similar treatment of rats with DOCA alone did not. The onset of hypertension and increased COP of tail vessels in the rats so treated with aldosterone was usually delayed by 4 or more days. To define more precisely the time course of the changes in blood pressure and COP induced by aldosterone hypertension was induced in rats by continuous subcutaneous infusion of aldosterone in an alcohol – 5% dextrose in water vehicle. Under these circumstances the rise in blood pressure and COP occurred after a delay of 2 days when measured after ganglionic blockade. On termination of the infusion the hypertension was rapidly reversed, the blood pressure declining smoothly to normal levels within 7 days.These results confirm that aldosterone alone can in fact induce hypertension in rats and suggest that the mechanism(s) by which aldosterone produces hypertension may differ in certain important respects from that involved in DOCA hypertension.
A new chronically cannulated carotid artery preparation for determination of drug half-lives in guinea pig
Authors: Latham A. N.
Published: April 2011

A reliable procedure for implanting a cannula into the carotid artery of the guinea pig is described. The gaseous anaesthetic used provided excellent control, rapid recovery, and caused no fatalities. There was no evidence of postoperative infection and patency of the cannula could be maintained for 21 days after surgery. There was no indication of postoperative trauma and removal of blood appeared to be painless.Efficacy of the preparation was demonstrated by repeated removal of 3-ml volumes of blood for the determination of the half-life of phenobarbital acutely in five animals and chronically in three guinea pigs treated with the drug for 14 days. Administration of pheobarbital twice daily (20 or 50 mg/kg, ip) for 1 week increased its clearance rate fivefold. Treatment for an additional week produced a further increase in pheobarbital clearance. The cannulated guinea pig preparation described should allow determination of the pharmacokinetics of many drugs in this species.
Thermoregulatory effects of methoxamine and isoprenaline following injections into the cerebral ventricles of conscious rabbits
Authors: Jones D. L. , Veale W. L. , Cooper K. E.
Published: April 2011

There is evidence to suggest that within the hypothalamus noradrenaline (NA) is an inhibitory neurotransmitter acting on both the heat production and heat loss pathways in the rabbit. Further, it has been proposed that the inhibition of the heat loss pathway which results in hyperthermia is mediated primarily through α-adrenergic receptors within the anterior hypothalamic–preoptic area. We have investigated the effects of the α-receptor agonist methoxamine, administered directly into the cerebral ventricles, on body temperature at various ambient temperatures in both the shorn and unshorn rabbit. At all ambient temperatures tested, administration of methoxamine into a lateral cerebral ventricle produced a gradual dose-dependent hyperthermia. The magnitude of the hyperthermic response diminished with decreasing ambient temperatures. It is already known that the β-adrenergic agonist isoprenaline produces little or no effect on body temperature following intracranial application at ambient temperatures above 18 °C. In our experiments conducted at the lower ambient temperature, it produced a pronounced dose-dependent fall in body temperature in the shorn rabbit. The results of this work support the suggestion that NA can act as an inhibitory substance on the heat production or heat loss pathway in the rabbit. Which pathway is inhibited at any one time is dependent on the ambient temperature. Further, it would appear that inhibition of the heat loss pathway is largely mediated through α-adrenergic receptors, whilst the inhibition of the heat production pathway is mediated to a large extent through β-adrenergic receptors.
Study of reversibility of effects of hypoxia in airway smooth muscle
Authors: Stephens Newman L.
Published: April 2011

We have shown in the past that hypoxia impairs contractile activity in tracheal smooth muscle (TSM). This was associated with partial uncoupling of mitochondria. It remained to be determined whether these changes were reversible. The TSM model was felt to be superior to the isolated mitochondria since it was likely to be free from artefacts inherent in procedures involving homogenisation and extraction. We report here that the oxygen uptake rates of the isolated, mechanically active TSM were increased in the posthypoxia recovery period when compared with the prehypoxia active muscle. Mechanical recovery was complete.
Compensatory renal hypertrophy. I. Evidence for a factor of renal origin inhibiting DNA synthesis
Authors: Martel-Pelletier J. , Bergeron M.
Published: April 2011

This study describes a method for the measurement and partial purification of a factor seemingly involved in the regulation of the renal mass.After homogenization at 4 °C, rabbit kidneys were centrifuged for 100 min at 105 000 g. The resulting supernatant (S-105) was lyophilized and tested on kidney slices obtained from rats mononephrectomized 48 h previously. We have developed a method based on the inhibition of DNA synthesis to measure the activity of the S-105. Slices of renal cortex, undergoing compensatory hypertrophy, were incubated in vitro in Hanks' medium at 37 °C, pH 7.4, in an O2–CO2 atmosphere in the presence of 0.144 μg (20 μCi (1 Ci = 37 GBq)) [3H]thymidine.An inhibition of DNA uptake of [3H]thymidine was noted in the presence of S-105. When other media (Hanks', sucrose, water) were used to extract S-105, the same type of inhibition was noted even though the sucrose buffer seemed ideal for the preservation of the inhibitory factor. The inhibitory effect was still observed after dialysis of S-105 against membranes permitting exclusion of molecules with molecular weight smaller than about 4000 (such as electrolytes and tissue thymidine). This inhibition seems to be specific, since other tissues such as liver in regeneration and rat intestine were not influenced by the dialyzed renal S-105. The dialyzable fraction did contain some inhibitors, but they were not specific for the kidney since they also acted on the liver and the jejunum.Our results suggest the existence, in the normal nephron, of a specific inhibitor of thymidine incorporation into DNA of kidneys undergoing a compensatory hypertrophy. This renal factor has a molecular weight of over 5000.
The effects of glucose and insulin on contraction of the isolated diaphragm
Authors: Mainwood G. W. , Cechetto D. , St. Jean Monique
Published: April 2011

High glucose concentrations (55 mM) were found to suppress the isometric contraction tension of rat diaphragm. The effect appears to be due to the resulting transmembrane osmotic gradient in spite of the fact that glucose uptake by the diaphragm is fairly rapid. Insulin can reverse the effect of hypertonic glucose to a considerable extent. The problems of estimating intracellular glucose concentration in the isolated muscle are considered. Estimates of intracellular glucose taking into account extracellular space and extracellular diffusion gradients were made using a two-compartment model. Calculations based on the model show that in the presence of insulin, intracellular glucose increases from about 1 to 19 μmol/ml of muscle fibre. The mean transmembrane glucose concentration gradient decreases from 41 to 18 μmol/ml. With the use of the model it appears possible to relate most of the observed effect of glucose and insulin on isometric contraction to their influence on the osmotic gradient across the muscle fibre membrane. Insulin appears to have some additional effects on muscles suppressed by hypertonic solutions which are not accounted for by this mechanism.
Resistance to heat stress in the spontaneously hypertensive rat
Authors: Wright G. , Iams S. , Knecht E.
Published: April 2011

Thermal resistance as determined by survival time was examined in different age groups of spontaneously hypertensive (SHR) rats during terminal heating. A comparison with age or weight matched controls indicated that the thermal resistance of SHR animals was markedly inferior to that of normotensive animals as evidenced by 56% and 36% decreases in the total heating time to the lethal temperature, respectively. The decrease in thermal resistance in SHR animals occurred after 8 weeks of age and was coincident with the elevation of mean blood pressure to about 150 mmHg. The observation of significantly decreased total body water and rates of evaporation at critical colonic temperatures (39–40 °C) suggested the possibility of a reduced ability for water mobilization for thermoregulatory purposes in hypertensive animals although it appeared that other factors affecting heat gain or loss were involved.
The effects of calcium deficiency on the electrical activity of Nitella flexilis
Authors: Netten C. Van , Belton P.
Published: April 2011

Calcium chelators such as ethylenediaminetetraacetic acid and sodium citrate produce repetitive activity and prolong the spike of internodal cells of Nitella flexilis. Removal of Ca2+, Mg2+, Na+, and K+ from the outside of the cell by washing the preparation with Tris propionate or Tris chloride hyperpolarizes the cells but does not initiate repetitive activity or increase the duration of the spike appreciably. It was concluded that cell-bound Ca2+ controls the threshold for stimulation and the duration of the spike, and that the removal of Ca2+ from the cell membrane, either by chelation or displacement, changes the normal behaviour of the cell by altering its permeability to some other ion or ions.
Salvage of adenosine, inosine, hypoxanthine, and adenine by the isolated epithelium of guinea pig jejunum
Authors: Kolassa N. , Stengg R. , Turnheim K.
Published: April 2011

The metabolism of adenosine, inosine, hypoxanthine, and adenine (labelled with 14C in the carbon 8 position) at a concentration of 5 × 10−6 M was studied in isolated epithelium of guinea pig jejunum. When adenosine or adenine was added to the antiluminal side of the epithelium, two-thirds or one-half, respectively, of cellular radioactivity was incorporated into the nucleotide fraction, mainly in the form of adenine nucleotides. Nucleotide synthesis from inosine or hypoxanthine was significantly smaller than that from adenosine. By contrast, another metabolic pattern was found after luminal administration of adenosine, inosine, or hypoxanthine: the incorporation rate into the nucleotide fraction was equally high and the label was recovered in IMP and adenine nucleotides to about the same extent with all three substrates. Purine riboside (10−4 M) significantly depressed nucleotide formation from adenosine, with respect to IMP formation in particular, while no change was observed in inosine or hypoxanthine salvage. The results suggest compartmentation of the enzymes of purine metabolism within the intestinal mucosa. The significance of this conclusion with regard to the salvage pathway is discussed.
Changements biochimiques dans le magnum de caille au cours du cycle ovulatoire. Role des hormones stéroïdes endogènes
Authors: Laugier Christian , Brard Emile
Published: April 2011

As the developing egg passes along the magnum, more than 80% of the soluble proteins and ovalbumin are released in the lumen and the RNA per milligram of DNA decreases by 31%. This discharge of the secretory goblet cells occurs only in the part of the magnum directly in contact with the yolk. The formation of egg white proteins during the cycle is in two stages. First there is a short period following the release of albumen when the synthesis of ovalbumin is very rapid at the beginning and then decreases to a minimum 5 h after oviposition. Secondly, from 5 h after oviposition to the next discharge of the glandular cells, the concentration of ovalbumin per cell unit increases with a rate of synthesis (Sov) equal to 0.218(t – 7) + 1.119 (Sov, milligram per milligram of DNA; t, number of hours after oviposition). The qualitative analysis of the ovalbumin shows that it is the fraction of dephosphoovalbumin which is synthesized first. It is quickly transformed into diphospho- and triphosphoovalbumin.

By surgical removal (4 h after oviposition) of the post ovulatory follicle (Fr) and the F1 follicle, which are responsible for the preovulatory peak of progesterone, or of F2, F3, and F4 follicles, which are responsible for the preovulatory peaks of estrogen and testosterone, a dramatic inhibition of the rate of egg-white protein synthesis is induced.
Metabolic clearance rate of adrenocorticotropin in the rat
Authors: Lalonde Josée , Normand Maurice
Published: April 2011

The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40–2560 μU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalarno–pituitary–adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.
Variability in development of tolerance to repeated injections of low doses of dl-amphetamine in rats
Authors: Thornhill J. A. , Hirst M. , Gowdey C. W.
Published: April 2011

Male albino rats received injections of saline for 5 days before and 5 days after a series of 10 daily injections of dl-amphetamine, 1 or 5 mg/kg, sc. Core temperatures were measured every 30 min for 4 h after each injection and feeding activity (on a CRF operant schedule) every 30 min throughout. After amphetamine at either 0800 or 2000 h, a dose-related hyperthermia, stereotypic behavior, and an initial inhibition of feeding occurred. This anorexia decreased over the 4-h post injection period only in the evening-injected rats receiving 5 mg/kg. Mean body weights of all groups continued to increase during amphetamine administration. Mean 24-h food intake tended to remain below that in the control period and the hyperthermic response did not change significantly in any group. Initially on withdrawal from amphetamine all groups showed 'rebound' feeding. Taken with earlier reports, these results suggest that tolerance development to amphetamine-induced anorexia, hyperthermia, and stereotypic behavior occurs at different rates and is dependent upon frequency, route, dose, time, the amphetamine used, and whether the diet was restricted.
Loss of body fat during an arctic winter expedition
Authors: O'Hara W. J. , Allen C. , Shephard R. J.
Published: April 2011

Fifty-five soldiers have been observed over a vigorous 10-day sledging patrol in the Canadian arctic and subarctic. Initial observations showed a low level of physical fitness (26% body fat, aerobic power 41.9 ± 7.8 ml kg−1 min−1, handgrip force 43.7 ± 7.2 kg). Over the 2-week northern sojourn, energy expenditures as measured by a Kofranyi–Michaelis respirometer and diary observation averaged 3248 kcal (13.6 MJ) day−1, with a small (152 kcal (633 kJ)) positive daily energy balance. A weight loss of 1 kg, presumably water, was made good within 1 week of return to the south. A fat loss of some 3.9 kg was probably attributable largely to the demands of lean tissue synthesis. The lean mass was increased by 3.9 kg over the trial, with parallel gains of muscle force and aerobic power. The rapid mobilization of depot fat led to marked ketonuria.
Receptors for bradykinin in intestinal and uterine smooth muscle
Authors: Barabé J. , Drouin J.-N. , Regoli D. , Park W. K.
Published: April 2011

An attempt has been made to characterize receptors for bradykinin (BK) in two smooth muscle preparations (cat ileum and rat uterus) sensitive to BK. Studies have shown that contractions of the two isolated organs produced by BK result from a direct action of this peptide on specific receptors. Since (a) experimental dose–response curves of BK in the two preparations are superimposed to the theoretical ones calculated with the equation of Clark (Clark, A. J. 1937. General pharmacology. Verlag von J. Springer, Berlin), (b) ratios between doses producing 16 and 84% of maximum effect correspond to 1:28 (cat ileum) and 1:19 (rat uterus), and (c) relations stimulus–effect are linear and with a slope of 1.0 (cat ileum) and 1.1 (rat uterus), we choose to interpret these findings with the approach proposed by Clark (1937) and elaborated by Ariens (Ariens, E. J. 1964. Molecular pharmacology. Academic Press Inc., London).Studies on the structure–activity relationships performed with fragments and analogues of BK do not allow for a precise distinction of groups responsible for affinity or for the activation of receptors, and actually show that 1-Arg, 4-Gly, 5-Phe, 8-Phe, and 9-Arg are essential for the interaction. Analogues more potent than BK were obtained by replacing 8-Phe with Tyr(Me) and Trp, while 8-Cha BK keeps full activity. When tested for antagonism, all the analogues and the fragments are inactive; some of these compounds were found to potentiate the activity of BK in the rat uterus.Cyproheptadine (CH), dihydrochlorprothixene (DHCP), phenylalanine-octyl ester (POE), and β-phenylanaline-hexyl ester (β-PHE), as well as 5-Tyr(Me),8-Tyr(Me) BK, and 8-Leu-OMe Octa BK were tested for antagonism. CH, DHCP, POE, and β-PHE (at concentrations ranging from 10−6 to 10−5 M) reduce the myotropic effects of BK in the two preparations. The antagonism is nonspecific for BK, since the effects of other agonists acting on receptors different from those of BK are also reduced. Maximal responses to BK as well as to the other stimulants are significantly diminished, indicating that the antagonism is of the noncompetitive type. 5-Tyr(Me),8-Tyr(Me) BK and 8-Leu-OMe Octa BK did not exert any antagonistic action.Evidence is presented in favour of the interpretation that the receptors for BK in the two preparations are of the same type, and differ from the receptor of the rabbit aorta.
The role of prostaglandins in hypertension. I. The release of prostaglandins by aorta strips of renal, DOCA–salt, and spontaneously hypertensive rats
Authors: Rioux F. , Quirion R. , Regoli D.
Published: April 2011

The release of prostaglandin-like (PG-like) material by aorta strips of normotensive and hypertensive rats has been studied in vitro. When incubated in an oxygenated Krebs solution kept at 37 °C, aorta strips removed from 8- and 12-week-old spontaneously hypertensive (SH) rats generate 1.2–2.5 times more PG-like material than aorta strips from age-matched normotensive Wistar (NW) rats. The overproduction of PG-like material by aorta strips of SH rats did not precede the development of hypertension in SH rats. Aorta strips derived from renal and DOCA–salt hypertensive rats produced 1.5–3 times more PG-like material than aorta strips from NW rats. The production of PG-like material by aorta strips of renal and DOCA–salt hypertensive rats was largely reduced when hypertension was interrupted in these animals, thus suggesting that the alteration taking place in the arteries of hypertensive rats (namely increased production of PGs) during the development of hypertension was reversible. The production of PG-like material by aorta strips of hypertensive rats was inhibited by indomethacin.Analysis of the PG-like material by bioassays and thin-layer chromatography suggests the presence of PGE2 and PGE1. The possible involvement of these PGs in the pathogenesis of hypertension in rats is discussed.
The calcium–magnesium interaction in the process of release of noradrenaline by nicotine
Authors: Jayasundar S. , Vohra M. M.
Published: April 2011

The calcium–magnesium (Ca2+–Mg2+) interaction in the process of nicotine-induced release of [3H]noradrenaline ([3H]NA) from rat isolated vas deferens was studied. Increasing extracellular concentrations of Mg2+ caused a dose-dependent depression of release of [3H]NA by nicotine, and this inhibitory effect of Mg2+ was overcome by raising the concentration of Ca2+. It is concluded that Mg2+ antagonizes the nicotine-induced increase in the Ca2+ influx into the adrenergic nerve terminals, and that nicotine acts on adrenergic neuronal membrane rather than intraneuronally to cause release of NA.
Presynaptic depression of synaptic response of Renshaw cells by adenosine 5′-monophosphate
Authors: Lekić D.
Published: April 2011

The action of AMP (adenosine 5′-monophosphate) on synaptic transmission of Renshaw cells has been studied in cats under Dial anaesthesia. AMP applied iontophoretically reversibly reduced synaptic responses of Renshaw cells evoked by stimulation of ventral roots, as well as their spontaneous firing; however, there were no marked effects on discharges of these cells caused by iontophoretic application of acetylcholine, aspartate, and glutamate. On the other hand, AMP had no comparable effect on synaptic responses of dorsal horn interneurones evoked by stimulation of dorsal roots or their spontaneous discharges.
The effects of cholecystokinin and cholecystokinin-octapeptide on intestinal lymph flow in the rat
Authors: Turner S. G. , Barrowman J. A.
Published: April 2011

Intravenous cholecystokinin and its synthetic C-terminal octapeptide were found to cause a transient augmentation of intestinal lymph flow in the rat. Concomitant increase in lymph protein transport suggests that this reflects the increase in intestinal blood flow which is known to occur in response to these agents.
Calcium influx and spontaneous phasic contractions of portal veins after treatment with reserpine, 6-hydroxydopamine, and cocaine
Authors: Kaiman M. , Shibata S.
Published: April 2011

Reserpine treatment increased the amplitude of the spontaneous phasic contraction (SPC) of portal veins obtained from rabbit and guinea pig but did not alter that of rat. The amplitude of the SPC of portal veins from these animals was increased after 6-hydroxydopamine (6-OHDA) but was not changed after cocaine treatment. Reserpine-and 6-OHDA-induced changes in portal vein SPC amplitude were accompanied by an increase in 45Ca influx.These results indicate that the elevation in SPC amplitude is accompanied by an increase in calcium influx.
The effects of acute hypercapnia on cerebral indole amine metabolism
Authors: MacMillan V.
Published: April 2011

The effects of 1-h exposure to hypercapnia ([Formula: see text], 90–110 mmHg) on cerebral indole amine metabolism were studied in rats by measurement of cerebral hemisphere contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA). 5-HIAA content was increased after 1-h exposure to hypercapnia, whereas tryptophan, 5-HTP, and 5-HT remained unchanged from control. The accumulation of 5-HTP after decarboxylase inhibition with 3-hydroxybenzyl hydrazine was increased in hypercapnic rats and indicated an increased activity of tryptophan hydroxylase. During the 1-h exposure to hypercapnia there was increased accumulation of 5-HT after monoamine oxidase inhibition with pargyline and increased accumulation of 5-HIAA arter probenecid. The results indicate an increased synthesis and degradation of indole amines in acute hypercapnia.
Effect of acute blood volume expansion on cardiac output, plasma dopamine β-hydroxylase, and renal function in rats with chronic constriction of the ascending aorta
Authors: Wong J. H. , Baines A. D.
Published: April 2011

To examine the effect of raised left atrial pressure (AP) on the relationship of cardiac output to renal function, we constricted the ascending aorta in rats (AC) and 1–6 months later tested their response to acute volume expansion (VE) with blood (2% body weight, iv). Sham-operated (SH) rats were controls. In AC rats heart weight increased 38%, but cardiac output was 47% lower. Statistically significant differences in the initial clearance periods were (AC vs. SH): venous pressure (VP) 8 ± 2 vs. 3 ± 1 cm H2O; inulin clearance (CIN) 0.61 ± 0.06 vs. 0.84 ± 0.04 ml/min; sodium excretion (UNaV) 1.2 ± 0.2 vs. 2.1 ± 0.3 μequiv./min. Filtration fraction, fractional UNaV, mean arterial pressure (MAP), and plasma dopamine β-hydroxylase (DBH) were the same in both groups. After VE, cardiac output increased proportionately more in AC (69% vs. 27%); however, the absolute increases were not different. UNaV increased proportionately more in AC rats, but the absolute increase was less (5.1 vs. 7.5 μequiv./min). Multiple variable regression analysis showed that UNaV correlated with CIN, MAP, and VP, with no difference between AC and SH animals. Cardiovascular–renal relationships were indistinguishable from previous descriptions of dogs and rats with chronic vena caval constriction. Modulation of renal function by left AP was not apparent. In both groups after the peak response to VE, UNaV decreased in association with decreased cardiac output and increased sympathetic nervous activity as indicated by raised DBH levels. After VE, VP remained high in AC but not in SH animals.
Effects of clofibrate on plasma tryptophan, growth hormone, and prolactin and on brain tryptophan and serotonin in prepubertal rats
Authors: Tache Yvette , Letarte Jacques , Collu Robert
Published: April 2011

The effects of clofibrate administration (200 mg/kg, po) on somatic growth, plasma levels of lipids, tryptophan, growth hormone (GH), and prolactin (PRL), as well as on brain concentrations of tryptophan and 5-hydroxytryptamine (5-HT) were studied in prepubertal male rats. The drug did not significantly alter ponderal growth, but an appreciable reduction of tail length was observed in rats treated for 30 days. Triglyceride concentrations in plasma showed a 43% diminution after 30 days of treatment, whereas free fatty acid (FFA) levels were not modified. Clofibrate administration for 7, 15, or 30 days caused a fall in total tryptophan and a significant increase of the free fraction in plasma with no change in brain tryptophan levels. Brain 5-HT was generally unaffected but a marked elevation of this parameter was noted in rats treated for 15 days. Plasma GH and PRL concentrations remained unaltered. It may be concluded from these findings that the slight reduction of somatic growth, the diminution of triglycerides, and the increase of free tryptophan in plasma, induced by chronic clofibrate treatment, are not associated with variations in brain tryptophan and 5-HT levels or with modifications of plasma GH and PRL titers.
Hemostatic changes induced by exercise during oral contraceptive use
Authors: Hedlin Anne M. , Milojevic Susan , Korey Andrew
Published: April 2011

Exercise-induced changes in hemostatic measurements were studied in 25 women. Twelve of the subjects were not using oral contraceptives and the remainder were using Demulen (ethynodiol diacetate (1 mg) and ethinyl estradiol (0.05 mg)). Exercise on a treadmill induced similar changes in both groups, but during the use of Demulen the levels of fibrinogen and plasminogen were higher, antithrombin level was lower, and the recalcified clotting and dilute whole blood lysis times were shorter in group 2 than in the corresponding samples obtained from the nonpill users.
Effects of 6-hydroxydopamine on brain and blood catecholamines, ammonia, and amino acids in rats
Authors: Singh A. K. , Banister E. W.
Published: April 2011

The effect of 6-hydroxydopamine (6-OHDA) upon brain and blood catecholamines, ammonia, and amino acids has been studied in rats subjected to increasing doses of the drug. Time dependent effects after injection have also been studied. Systemically injected 6-OHDA significantly, acutely reduced brain adrenaline (A), noradrenaline (NA), total catecholamines (TC), γ-aminobutyric acid (GABA), and glutamic acid (Glu); concomitantly brain ammonia (NH3) increased. In blood, NA and TC were reduced and A and NH3 increased. The changes in brain monoamines are surprising since it has been reported that 6-OHDA does not cross the blood-brain barrier. We have proposed that these changes result from a general stress response or a reflex peripheral sympathetic response to falling blood pressure which in some manner communicates to the central nervous system. As the dose of 6-OHDA increased, brain NH3 increased and Glu decreased. A similar effect was seen from a single dose as the time after injection for sampling brain and blood constituents increased. Blood ammonia increases without change in Glu, glutamine, or asparagine. The source of NH3 may be from deamination of adenine nucleotide or catechols released from nerve terminals under the abnormal stimulus of 6-OHDA.
Dissociation of cyclic GMP synthesis from cholinergic-stimulated secretion of protein from rat exocrine pancreas
Authors: Heisler Seymour , Lambert Michel
Published: April 2011

The phosphodiesterase inhibitors RO-201724/1 and 1-methyl-3-isobutylxanthine (MIX) stimulate a rapid increase in cyclic GMP content in rat pancreas; the latter agent also potentiates the stimulatory effect of carbachol on cyclic GMP synthesis. However, neither RO-201724/1 nor MIX alter basal secretion of 3H-labeled protein, nor do they affect the secretory response to carbachol used in either suboptimal or optimal concentrations. MIX as well does not alter the rate at which carbachol stimulates pancreatic enzyme release. The ability of carbachol to increase cyclic GMP synthesis is lost if extracellular calcium concentration is lowered to 0.05 mM; at this calcium concentration, however, the muscarinic agent still elicits a marked secretory effect. The dissociation between cyclic GMP synthesis and the secretory response suggests that the cyclic nucleotide does not play a major role in the stimulus – enzyme secretion coupling phenomenon of the exocrine pancreas.
Changes in the hyperthermic responses of rats to daily injections of morphine and the antagonism of the acute response by naloxone
Authors: Thornhill J. A. , Hirst M. , Gowdey C. W.
Published: April 2011

Core temperatures of unrestrained male rats were measured by rectal probe over a 4-h period following seven daily subcutaneous injections of morphine sulphate in doses of 5, 20, or 80 mg/kg. With the smaller doses, rapid hyperthermia occurred and was maximal after 20 mg/kg; with 80 mg/kg, two of eight rats had immediate hypothermia, with the group response being a small, delayed hyperthermia. The results with repeated administration of morphine give statistical validity to earlier findings suggesting that peak hyperthermia increased and occurred progressively sooner after each injection of morphine. In groups of naive rats a single injection was given of saline or of 1, 10, or 40 mg naloxone hydrochloride per kilogram in saline. In these rats saline led to a slight increase in core temperature; when the first injection was one of the three doses of naloxone, no transient increase was seen. In nine other groups each of the three doses of naloxone was given 15 min before each of the morphine doses. All three doses of naloxone significantly reduced the hyperthermia induced by 5 and 20 mg morphine sulphate per kilogram, but this was less apparent in the group treated with 80 mg/kg, although naloxone at 40 mg/kg prevented any increase in temperature for over 3 h. The results obtained in this study demonstrate that morphine-induced temperature changes and perhaps stress-induced changes can be suppressed by naloxone.
Effects of arachidonic acid and indomethacin on the in vitro release of prostaglandins by aortic strips of spontaneously hypertensive rats
Authors: Quirion R. , Rioux F. , Regoli D.
Published: April 2011

Aortic strips removed from spontaneously hypertensive (SH) rats and preincubated with arachidonic acid (1.0 × 10−5 g/ml) for 15 min produced two times more prostaglandin (PG) like material than aortae unexposed to the precursor of PG biosynthesis. The stimulating effect of arachidonic acid was largely inhibited by indomethacin (1.0 × 10−5 g/ml). Also, the release of PG-like material by aortic strips derived from SH rats treated with an intravenous injection of indomethacin (10 mg/kg) was inhibited by 74% compared with the control tissues. These results raised the possibility that the in vivo conversion of arachidonic acid by large arteries of SH rats may contribute to the hypotensive effect of this PG precursor in SH rats.
The effect of glucagon on intestinal lymph flow in rats
Authors: Barrowman J. A. , Kwan P. , Mousseau C. , Turner S. G.
Published: April 2011

Intravenous injection of a bolus of 5 μg of glucagon to rats with an intestinal lymph fistula produces a marked, transient rise in lymph flow and protein output from the fistula. The effect is presumably the result of brief enhancement of splanchnic blood flow.
Opiate properties of SKF 525A
Authors: Ho T. K. , LaBella F. S. , Pinsky C.
Published: April 2011

SKF 525A, a classical inhibitor of microsomal drug-metabolizing enzymes, is structurally similar to the diphenylpropylamine analgesics, and certain reported effects in animals resemble those produced by opiate drugs. In an opiate radioreceptor assay, SKF 525A was 50 times less potent than methadone in the absence of sodium and 10 times less potent in the presence of sodium. The nature of the sodium effect indicates SKF 525A to have less opiate agonist character than does methadone. In mice, 2 mg of SKF 525A given intraperitoneally induced less profound analgesia on a hot plate (44 °C) than did 0.1 mg of methadone. Analgesia by SKF 525A was prevented by pretreatment of the mice with naloxone. In rats, 50 μg of SKF 525A given intracerebroventricularly was analgesic.
The effects of vasodilators in the perfused hind limbs of spontaneously hypertensive and normotensive rats
Authors: Deragon G. , Regoli D. , Rioux F.
Published: April 2011

The vascular effects of isoproterenol and nitroprusside were evaluated in the perfused hind limbs of age-matched normotensive Wistar (NW) and spontaneously hypertensive (SH) rats. The vasodilating effects of these two compounds were assessed in the presence of concentrations of noradrenaline sufficient to raise the basal perfusion pressure to 85–110 mmHg. The sensitivity of the hind limb vessels of SH rats to the vasodilating action of isoproterenol (2.4 × 10−6–1.0 × 10−4 M) was slightly greater than that of the hind limb vessels of NW rats. On the other hand, the sensitivity to the vasodilating effect of nitroprusside (1.7 × 10−7–3.3 × 10−5 M) was similar in the hind limb vessels of both groups of rats. Propranolol (7.6 × 10−6 M) inhibited to a similar extent the isoproterenol-induced dilation of NW or SH hind limb vessels, but did not modify the vasodilating effect of nitroprusside in these preparations, thus suggesting that the vasodilating action of isoproterenol was due to the stimulation of vascular β-adrenergic receptors. These results do not support the hypothesis suggesting the existence of a deficient vascular relaxation in hypertensive rats.
Muscarinic inhibition of endogenous myocardial catecholamine liberation in the dog
Authors: Lavallée Michel , Champlain Jacques de , Nadeau Réginald A. , Yamaguchi Nobuharu
Published: April 2011

The release of endogenous catecholamine (CA) into the coronary sinus of the anesthetized dog was investigated under basal sympathetic tone and during sympathetic and vagal electrical stimulation. Under basal conditions, right distal cervical vagal stimulation (1, 2, 4, 8, 16 Hz) did not significantly alter the output of CA into the conorary sinus although important increases in aortic CA levels were observed. Stimulation of the right cardioaccelerator nerves (10 Hz) caused a marked and reproducible increase in coronary sinus CA levels but this effect could be progressively attenuated by superposing vagal stimulation at increasing frequencies. A maximal inhibition (66%) of CA liberation was observed at a vagal stimulation frequency of 16 Hz. Atropine (2 μg/kg) blocked selectively the effect of low frequency vagal stimulation. Methacholine (3 μg/kg per minute) infusion mimicked vagal inhibition on CA liberation. It is suggested that a functional vagal inhibition of sympathetic CA liberation could be mediated through activation of presynaptic muscarinic receptors located on the adrenergic fibers within the left ventricle of the dog; moreover, the excellent correlation observed between the decrease in CA liberation and the first derivative of left ventricular pressure (dp/dt) suggests that this inhibition is of physiological significance. Such mechanisms could be implicated in the local fine adjustments of neurotransmitter liberation and in the functional peripheral integration of both components of the autonomic nervous system.
The role of renal nerves in the response to dipsogenic stimuli in the rat
Authors: Sharpe Michael D. , Mogenson Gordon J. , Calaresu Franco R.
Published: April 2011

The effect of bilateral renal denervation on water intake and urine volume during specific thirst challenges was studied in rats. Renal denervation attenuated significantly the drinking response elicited by the administration of 30% polyethylene glycol (PG, extracellular challenge) but had no effect on the drinking response after an intracellular challenge (2.5 M NaCl) or after a 24-h water deprivation period. Furthermore, during a PG challenge total water intake was the same in two groups of rats, one with denervated kidneys and the other with β-adrenergic neural activity in efferent renal nerves eliminated by blocking agents. Urine volumes were not affected by PG administration or water deprivation in denervated rats but were increased significantly after administration of 2.5 M NaCl. These results indicate that renal nerves play an important role in the physiological processes controlling extracellular thirst, and suggest that this role may be related to the neural control of release of renin.
Effect of oxytocin on estrogen-induced uterine luminal fluid accumulation in ovariectomized rats and the role of prostaglandins
Authors: Kennedy T. G.
Published: April 2011

In estrogen-treated ovariectomized rats, uterine luminal fluid accumulation has been used as an indirect measure of cervical tone, with loss of luminal fluid being interpreted as indicating reduced tone. Since the recently reported ability of analogues of prostaglandins E2 and F2α to cause loss of luminal fluid might have resulted, not from reduced cervical tone, but from uterine contractions forcing fluid through constricted cervices, the effects of oxytocin, also a stimulator of myometrial activity, on luminal fluid accumulation were investigated. When ovariectomized rats, implanted 72 h previously with a Silastic capsule containing 17β-estradiol, were given a single injection of oxytocin and killed 1–2 h later, oxytocin, in a dose-dependent fashion, reduced uterine luminal fluid accumulation. For a supramaximal dose of oxytocin, this effect was seen within 15 min. In rats in which one uterine horn was ligated at the cervical end, fluid accumulation in the ligated horns did not differ significantly in control and treated rats, whereas in nonligated horns, oxytocin reduced the fluid accumulation, suggesting that loss of fluid occurred through the cervix rather than by reabsorption. Given twice daily for 3 days commencing immediately after the insertion of the estrogen-containing capsule, oxytocin had no effect on luminal fluid accumulation in horns ligated at the cervical end, indicating that oxytocin did not inhibit luminal fluid formation. Prostaglandin biosynthesis did not appear to be essential for the acute effect of oxytocin since treatment of rats with indomethacin, although reducing uterine and cervical prostaglandin levels, did not inhibit the effect of oxytocin. However, loss of fluid occurred slightly sooner following oxytocin administration in controls than in indomethacin-treated animals. In addition, for animals autopsied 10 min after oxytocin injection, the dose–response relationship between oxytocin and uterine luminal fluid was affected by indomethacin treatment. These data suggest that prostaglandins act synergistically with oxytocin to bring about loss of uterine luminal fluid accumulation. However, the validity of the use of luminal fluid accumulation as an indicator of cervical tone remains to be resolved.
A study of carbachol–atropine interaction on intestinal smooth muscle vesicles, using a fluorescent probe
Authors: Spero L.
Published: April 2011

Plasma membrane vesicles were prepared from guinea pig ileum longitudinal muscle. The vesicles were characterized by electron microscopy and analysis of lipid and protein content. They were shown to be free of gross contamination from actomyosin, sarcoplasmic reticulum, and mitochondria. 8-Anilino-1-naphthalene sulphonic acid (ANS) binding characteristics were similar to those found on other membranes. Both carbachol and atropine increased the fluorescence of ANS bound to this membrane, the maximum increase for atropine being greater than that for carbachol. Since neither drug affected the apparent affinity constant for the ANS–membrane interaction, it may be assumed that the increased fluorescence was due to an increase in the number of ANS binding sites. The carbachol-dependent increase in ANS fluorescence was blocked noncompetitively by atropine but not by tubocurarine or diphenhydramine. These latter two antagonists also increased ANS fluorescence but at much higher concentrations than either carbachol or atropine. Neither atropine nor carbachol increased ANS fluorescence on either erythrocyte ghosts or liposomes (prepared from a lipid extract of the muscle membrane).