Quantitative aspects of granulocytic progenitor cell (CFUc) mobilization from extravascular sites in dogs using dextran sulphate (DS)

Abstract. The relationship between the increase in the blood CFUc concentration after intravenous injection of dextran sulphate (DS) and the pre-existing levels of spontaneously circulating CFUc was studied in dogs. After 15 mg DS/kg body weight the CFUc numbers per ml blood rose by a factor of 3.7 over the pre-injection values, from 78 ± 11 (SEM) to 359 ± 50, in normal dogs, and increased by a factor of 3.9 in 0.84-Gy-r-irradiated animals which had a reduced initial CFUc concentration per ml, from 35 ± 8 to 116 ± 43. The injection of 20 mg DS/kg body weight into unirradiated dogs caused an increase, by a factor of 11.5, of the pre-injection CFUc concentration, from 101 ± 20 to 921 ± 106. On the basis of the mobilization curves for individual dogs, a significant correlation was found between the normal blood CFUc value and the number of CFUc mobilized by DS for both dose levels. From the descending part of the mobilization curves obtained after 15 mg DS/kg body weight, kinetic parameters of canine circulating CFUc were derived. The mean blood transit time (τ) was 1.4 ± 0.5 hr and the half time ( T /2) was 1.0 ± 0.4 hr.     

Appearance of C-reactive protein (CRP) in serum and liver cytosol of cadmium-treated rats

The possibility of stimulation of C-reactive protein (CRP) due to inflammation and necrosis caused by cadmium was investigated. Cadmium injection (less than 3 mg/kg body weight) in white rat was found to be associated with the appearance of CRP in liver cytosol after 8 hr and in serum after 18 hr of injection. Although, no definite dose-response relationship was found, yet CRP level was elevated drastically, varying from 1-4 mg/g wet weight liver and 0.3-0.7 mg/ml serum. CRP-positive serum from Cd-treated rats precipitated with normal rat serum on agarose-covered slides in the presence of 1 mM CaCl2. Evidences for raised level of CRP indicates acute tissue damage in the animal.     

A comparison of chloride, bromide, and sucrose dilution volumes in neonatal pigs

Use of 36Cl, 82Br, and [3H]sucrose to estimate extracellular water volume was evaluated in 14 piglets (7-14 days old). 36Cl and 82Br were distributed in approximately the same volume, but a period of 5-6 hr after injection was required to reach equilibrium in the neonatal pig. Dilution volumes calculated before equilibration (2-5 hr) for 36Cl (326 +/- 11 ml/kg) and 82Br (328 +/- 13 ml/kg) were different from equilibration (6-8 hr) phase volumes (356 +/- 13 ml/kg and 355 +/- 13 ml/kg, respectively; P less than 0.001). A 3-hr sample estimated the same volume distribution calculated by extrapolation of the 6- to 8-hr period because of the relationship between the two slopes of the plasma clearance curves. After the 82Br and 36Cl had achieved equilibration, each was distributed in a volume equivalent to total body chloride space (362 +/- 29 ml/kg) measured by neutron activation; no statistical differences were found (P = 0.6). The early equilibration phase measured a 10% smaller, faster exchangeable fraction of total body Cl. Sucrose dilution volume (332 +/- 19 ml/kg) required multiple plasma samples for extrapolation and measured a dilution volume 7% smaller (P less than 0.05) than total body chloride space.     

Effects of sc administration of recombinant human insulin-like growth factor I (IGF-I) on normal human subjects

Recombinant human insulin-like growth factor I (IGF-I) was administered subcutaneously to each of 5 normal human subjects at doses of 0 mg/kg (control), 0.06 mg/kg, or 0.12 mg/kg successively at one week intervals. After 0.06 mg/kg or 0.12 mg/kg IGF-I injections, plasma IGF-I levels increased from 185 +/- 17 ng/ml (mean +/- SEM) to maximal levels of 396 +/- 21 ng/ml at 3 hours and from 169 +/- 14 ng/ml to 480 +/- 27 ng/ml at 4 hours, respectively. These two peak values were statistically different (p less than 0.05). After 0.06 mg/kg and 0.12 mg/kg IGF-I administration, blood glucose levels decreased from 85 +/- 2 mg/dl to minimal levels of 73 +/- 3 mg/dl at 3 hours and from 83 +/- 1 mg/dl to 50 +/- 4 mg/dl at 2 hours, respectively. These two minimal values were statistically different (p less than 0.001). Serum insulin and C-peptide levels were decreased in a dose dependent manner after IGF-I administration. There were no changes between blood urea nitrogen levels before and 4 hours after IGF-I administration. The urinary GH concentration decreased after 0.06 mg/kg IGF-I administration, but increased and maintained normal values after 0.12 mg/kg IGF-I administration.     

低分子量硫酸葡聚糖对小鼠造血干细胞动员作用的研究

给小鼠静脉注射低分子量（＜１０￣４ｕ）硫酸葡聚糖（ＤＳ）１５ｍｇ／ｋｇ后外周血中白细胞、单个核细胞（ｍｏｎｏｎｕｃｌｅａｒｃｅｋ,ＭＮＣ）、ＣＦＵ－ＧＭ、ＢＦＵ－Ｅ和ＣＦＵ－Ｍｉｘ产率等指标出现时相性变化。给药后１ｈ开始升高,２ｈ达到高峰、分别为药前值的２．２、２．６、３．８、４．４和３．０倍,７ｈ时趋向正常。给药后２ｈ上述各类细胞在外周血中的含量随着ＤＳ的剂量增加而增加。白细胞、ＭＮＣ计数在ＤＳ１８０ｍｇ／ｋｇ时达到峰值,均为对照组的４倍。２４０ｍｇ／ｋ８时未见明显增加。不同剂量ＤＳ对各系祖细胞均有不同程度的动员作用,ＤＳ剂量１５－３０ｍｇ／ｋｇ效果最好,每升血中ＣＦＵ－ＧＭ、ＢＦＵ－Ｅ、ＣＦＵ－Ｍｉｘ的数量分别相当于对照组的５．０、１１．９和８．８倍。其峰值出现时间与白细胞、ＭＮＣ不同,表明ＤＳ对不同类型细胞的作用机制也不尽一致。经口给小鼠投以ＤＳ２４０和４８ｏｍｇ／ｋｇ后,未见外周血中白细胞、ＭＮＣ计数有显著性升高,提示对造血干细胞没有动员作用。     

Oxygen uptake capacity of gills and skin in relation to body weight of the air-breathing siluroid fish, Clarias batrachus (Linn.).

Oxygen consumption through gills and skin in relation to body weight was estimated in the air-breathing catfish, Clarias batrachus, under two experimental conditions, viz., (i) when access to air was allowed and (ii) when air-breathing was prevented. There was a positive correlation between VO2 (ml/hr) and body weight in both experimental conditions. Oxygen consumption (ml/hr) increased by a power of 0.869 when access to air was allowed whereas the power was slightly less (b = 0.841) when air-breathing was prevented. As the values for exponent (b) were less than 1.0, the weight specific VO2 (ml/kg/hr) decreased with increasing body weight. The decrease was more marked (b = - 0.180) in fishes which were not allowed air than in those where access to air was allowed (b = - 0.148). Under normal conditions of water and air-breathing the rate of VO2 (ml/kg/hr) via gills and skin from water ranged from 39.7 +/- 3.21 to 76.7 +/- 9.01 and this increased to 42.17 +/- 6.2 to 105.9 +/- 8.33 when air-breathing was prevented. The increase in the rate of VO2 was perhaps associated with the increase in the volume of water irrigating the gills per unit time.     

Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in endotoxic shock.

We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free hemoglobin derived from human erythrocytes, on blood flow distribution and tissue oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium-anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin, followed by saline resuscitation to restore cardiac filling pressures to baseline levels. The animals were randomly divided into three groups: six served as control, six received DCLHb at a dose of 500 mg/kg (group 1) and six DCLHb at a dose of 1,000 mg/kg (group 2). Cardiac tamponade was then induced by saline injection in the pericardial sac to progressively reduce cardiac index and thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose-dependent vasopressor effect but did not significantly alter cardiac index or regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8 +/- 0.7 ml. kg(-1). min(-1) in the control group, but 8.6 +/- 0.9 and 8.2 +/- 0.7 ml. kg(-1). min(-1) in groups 1 and 2, respectively (both P < 0.05 vs. control group). The critical oxygen extraction ratio was 39.1 +/- 3.1% in the control group but 58.7 +/- 12.8% and 60.2 +/- 9.0% in groups 1 and 2, respectively. We conclude that DCLHb can improve whole body oxygen extraction capabilities during endotoxic shock in dogs.     

Systemic effect of chitin after intravenous administration to dogs

The systemic effect of chitin and chitin oligomer after intravenous administration was investigated in dogs by determining the chemiluminescence (CL) response and the white blood cell count (WBC). Chitin oligomer (2mg/kg) and physiological saline (5ml) did not have a systemic effect. However, in the dogs injected with chitin, WBC decreased significantly from 1 to 4 h after injection and then increased gradually to 1.4 times the pre-injection level at 72 h, while CL was significantly increased 1–2 h after injection.     

Effect of a long-lasting opioid receptor antagonist (naltrexone) on pulsatile LH release in early postpartum Holstein dairy cows

The present trial was the first one to investigate the effect of an intravenous injection of naltrexone, an opioid receptor antagonist that has a longer duration of action than that of naloxone, on the LH pulse in early postpartum Holstein dairy cows. On Day 10 postpartum, blood samples were collected from cows at 10-min intervals for a period of 4 h before (pre-injection period) and a period of 5 h after (post-injection period) an intravenous injection of 10 mL of saline (Control Group, n=5) or 300 mg of naltrexone in 10 mL of saline (Naltrexone Group, n=5). The plasma LH level was assayed by double antibody radioimmunoassay. The number of LH peaks per 1 h, the mean LH level, and the amplitude of LH peaks were analyzed utilizing the Pulsar algorithm, and data were compared by repeated measures ANOVA. No differences were observed in the parameters of LH pulse in the pre-injection period between the Control and the Naltrexone Groups (P>0.10). In the Naltrexone Group, the number of LH peaks per 1 h and the mean LH level were significantly higher in the post-injection period than in the pre-injection period (0.85 +/- 0.29 vs. 1.24 +/- 0.17, P<0.05, and 1.81 +/- 0.70 vs. 2.47 +/- 0.92 ng/ml, P<0.05, respectively), but there was no significant increase in the amplitude of LH peaks (1.48 +/- 0.64 vs. 1.83 +/- 0.82 ng/ml, P>0.10). In contrast, all of the parameters of LH pulse remained unchanged in the Control Group (P>0.10). These results suggested that an intravenous injection of naltrexone activates the LH pulse.     

Embryotoxicity of a single dose of medroxyprogesterone acetate (MPA) and maternal serum MPA concentrations in cynomolgus monkey (Macaca fascicularis)

A single dose of MPA (Depo-Provera; Upjohn Co., Kalamazoo, Michigan) was administered intramuscularly to 12 time-mated pregnant cynomolgus monkeys on day 27 (+/- 2) of gestation at 25 mg/kg or at 100 mg/kg. Maternal blood samples were collected immediately prior to MPA injection and then at regular intervals until cesarean section at term (day 152 +/- 3). Infants in both dose groups had external genital abnormalities. Female infants in the low-dose groups had partial or complete labial fusion, prominent median raphe, and clitoral hypertrophy; at high doses (100 mg/kg), the female infants had complete labial fusion and a distinct penile urethra. MPA had an opposite effect on external genitalia of male infants. The penis was short and the scrotal swelling was absent or less conspicuous, and two males had hypospadias. The adrenal glands were significantly smaller (P less than 0.05) in infants of both sexes treated with 100 mg/kg. One of the infants treated with 25 mg/kg of MPA had a muscular ventricular septal defect. Serum concentrations of MPA were determined by radioimmunoassay in eight pregnant monkeys. In the 25 mg/kg group the patterns of MPA profiles in the serum were similar in all four animals. An initial peak occurred at 24-48 hr postinjection (2.7-9.6 ng/ml), followed by a slight decrease at 3 days postinjection (gestational day 30), and then a steady increase to maximum levels of 10-14 ng/ml occurring between gestational days 37 and 50. Serum levels gradually declined to concentrations below 5 ng/ml by midgestation in three of four monkeys. By comparison, both the patterns and magnitude of MPA concentration showed great interanimal variation in the 100 mg/kg group. MPA was present in cord blood at measurable concentrations in infants at both dose groups; the levels ranged from 0.6 to 8.3 ng/ml, corresponding to 40-72% of the maternal concentrations. These results demonstrate that a single injection of MPA during early pregnancy causes selective embryotoxicity in both male and female fetuses. Presence of high levels of MPA in maternal sera during the critical period of genital development can cause specific genital defects; however, the exact mechanism by which MPA causes these paradoxical genital abnormalities is unknown.     

The effect of photoperiod on serum concentrations of luteinizing and follicle stimulating hormones in prepubertal heifers following ovariectomy and estradiol injection

Eleven heifers, between 63 and 197 days of age, were exposed to 18 hr light/day (L) or natural photoperiods (N), beginning October 19, 1979. They were ovariectomized 8 weeks later. LH concentrations after ovariectomy were not affected by photoperiod, but the rate of increase of FSH after ovariectomy was greater (P<0.10) for group L than for group N. Three weeks after ovariectomy, heiters were injected, IV, with 0.1 mug/kg estradiol-17beta. LH concentrations initially decreased after injection. This was followed by a series of pulses larger than those prior to injection. FSH concentrations declined after injection and remained low throughout the sampling period. The net response of LH concentrations to estradiol (mean post-injection concentration minus mean pre-injection concentration) was greater (P=0.05) for group L (4.7 +/- 0.49 ng/ml) than for group N (2.9 +/- 0.37 ng/ml). Photoperiod did not affect the net response of FSH concentrations to estradiol. We concluded that exposing prepubertal heifers to 18 hr light/day during the winter resulted in a greater rate of increase of FSH after ovariectomy and greater estrogen-induced LH release. Because the response of LH to estradiol-17beta differed from the response of FSH, these hormones may be regulated differently.     

Changes in plasma glucagon, pancreatic polypeptide and insulin during development of alloxan diabetes mellitus in dog

Changes in canine plasma glucose, immunoreactive glucagon (IRG), pancreatic polypeptide (PP) and insulin (IRI) were studied during the acute development of diabetes mellitus after iv alloxan injection. 100 mg or 75 mg/kg body weight of alloxan was injected iv and blood was taken successively till one or two days later. Plasma glucose showed four phases: first immediate and moderate decrease appeared 30 min after injection, second initial hyperglycemic phase, third hypoglycemic and fourth diabetic ones. Plasma IRI had already increased to 182 +/- 60 microU/ml 10 min after injection and again began to increase after about 6 h, peaking to 134 +/- 49 microU/ml at 18 h. Plasma IRG began increasing gradually soon after alloxan injection. The initial value was 196 +/- 26 pg/ml and it increased to 534 +/- 144 pg/ml at 4 h during the initial hyperglycemic phase, then reached a higher level through the hypoglycemic and diabetic phases. The change in plasma PP was similar to that in IRG. The initial value was 256 +/- 95 pg/ml at 12 h after injection, peaking to 840 +/- 100 pg/ml in the hypoglycemic phase. Similar blunted values were obtained following 75 mg/kg alloxan injection. Thus not only plasma IRI but also plasma IRG and PP varied greatly during the acute development of alloxan diabetes and some contribution of IRG to the initial hyperglycemic phase was suggested.     

ACTH-, glucose- and lactate-content of swine plasma during insulin-induced hypoglycemia]

The present investigation was undertaken to determine the content of ACTH, glucose and lactate in plasma of 4 pigs (body weight 82--118 kg) during a circadian period and during an insulin hypoglycemia test using 1 IU/kg in 3 pigs (body weight 96--118 kg) and 4 pigs (body weight 20--30 kg). The plasma ACTH level at rest was 57 +/- 27 pg/ml (Mean +/- SE) for all samples in all animals during a circadian period. Significant diurnal changes were not observed. During insulin-induced hypoglycaemia plasma ACTH rose from a mean (+/- SE) basal level of 35 +/- 15 to a maximum of 673 +/- 100 pg/ml at 60 min in heavier pigs and in lighter pigs to 395 +/- 153 at 30 min and 403 +/- 145 pg/ml at 120 min. Initial ACTH responses were evident 30 min (heavier pigs) and between 0 and 15 min (lighter pigs) after insulin administration. Plasma glucose decreased from a mean (+/- SE) basal level of 80 +/- 10 to a minimum of 6 +/- 1 mg/100 ml at 60 min (heavier pigs) and from 88 +/- 3 to 16 +/- 4 mg/100 ml at 60 min (lighter pigs). After its minimum level the glucose concentration showed a slower increment in the heavier pigs as compared to lighter animals. Plasma lactate rose from a mean (+/- SE) basal level of 19 +/- 10 to a maximum of 76 +/- 42 mg/100 ml at 120 min (heavier pigs) and from 12 +/- 3 to 37 +/- 16 mg/100 ml at 150 min (lighter group). In accordance with the changes in the blood plasma levels of ACTH, glucose and lactate, the clinical symptoms of hypoglycaemia in heavier pigs were more intensive.     

Effects of S-nitroso-N-acetyl-penicillamine administration on glucose tolerance and plasma levels of insulin and glucagon in the dog.

It has been suggested that nitric oxide (NO, nitrogen monoxide) is a regulator of carbohydrate metabolism in skeletal muscle. The present study was undertaken to investigate the acute effects of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) on blood glucose levels and on the gluco-regulatory hormones insulin and glucagon in healthy dogs. The acute effects of SNAP on mean arterial pressure and heart rate were also investigated. The drug was administered intravenously and the pre- and postprandial blood glucose, plasma insulin, and glucagon concentrations were determined at half-hour time intervals postadministration after a glucose challenge. The plasma nitrate and nitrite concentrations were measured and taken as the biochemical markers of in vivo NO formation. The oral glucose tolerance test revealed an impaired glucose tolerance in SNAP-treated dogs as reflected by the area under the glucose curve, 1150.50 +/- 63.00 mmol x 150 min and 1355.25 +/- 102.01 mmol/L x 150 min in dogs treated with 10 and 20 mg/kg of SNAP, respectively, compared with 860.25 +/- 60.68 mmol/L x 150 min in captopril-treated controls (P < 0.05). The 2-h blood glucose concentration in dogs treated with 20 mg/kg body wt of SNAP was 9.17 +/- 1.10 mmol/L compared with 5.59 +/- 0.26 mmol/L for captopril-treated controls (P = 0.015). The oral glucose tolerance test also confirmed an impaired insulin secretion in the SNAP-treated dogs. While the plasma insulin concentration increased gradually in the captopril-treated controls to a peak value of 39.50 +/- 2.55 microIU/ml, 1.5 h after a glucose challenge there was a decrease in the plasma insulin concentration in SNAP-treated dogs to a low value of 20.67 +/- 0.88 microIU/ml (P = 0.006). In contrast, there were no significant differences in plasma glucagon concentration in SNAP-treated dogs and captopril-treated dogs at any time points. Using the Griess reaction, we found that there was a 27-95% increase in plasma nitrate/nitrite concentration on administration of SNAP. The sustained hyperglycemic effect observed in SNAP-treated dogs was accompanied by a marginal decrease in the mean arterial blood pressure and a significant increase in heart rate (P < 0.05). We conclude that acute administration of SNAP in the oral glucose tolerance test releases NO that modulates the parameters of carbohydrate metabolism.     

Changes in plasma high-density lipoprotein cholesterol concentration after weight reduction in grossly obese subjects.

Changes in serum lipoproteins associated with weight loss were assessed in 13 grossly obese (relative weight 183%) patients who had participated in an outpatient semi-starvation diet consisting of liquid protein and carbohydrate. At the follow-up examination an average of six and a half months after the start of refeeding the mean weight loss was 16.1 +/- 4.5 kg or 15% of initial body weight. Significant increases in high-density lipoprotein (HDL) cholesterol of 0.16 +/- 0.05 mmol/l (6 +/- 2 mg/100 ml) and decreases in triglycerides (0.8 +/- 0.23 mmol/l; 73 +/- 20 mg/100 ml) and fasting blood sugar (0.6 +/- 0.22 mmol/l; 11 +/- 4 mg/100 ml) were observed. Changes in HDL cholesterol correlated significantly with changes in weight (r = 0.667) and percentage change in weight. The intercept of the regression equation relating HDL cholesterol to percentage change in weight was -7.3, indicating that a change in HDL cholesterol greater than zero required a weight loss of at least 7.3% of body weight. Thus, weight loss can significantly increase HDL cholesterol concentrations but a considerable amount of weight must be lost to produce a significant increase in HDL cholesterol concentration.     

Short-term immobilization of mice by methohexitone

The feasibility of short-term immobilization for <5 min of female mice by methohexitone sodium was studied. In C3H/Neu mice, methohexitone at a dose <40 mg/kg did not result in chemical restraint, doses >50 mg/kg caused considerable lethality. A dose of 44 mg/kg, applied intraperitoneally at a concentration of 6.46 mg/ml, is suitable for immobilization without complications. This concentration was chosen in order to achieve an injection volume of about 0.15 ml for a mouse with an average body weight of 22 g, corresponding to about 1 mg/mouse. Complete immobilization, defined as absence of the righting reflex, was observed within 3.3 +/- 0.8 min (mean +/- SD, n = 10) after the injection and lasted for 1.5 +/- 0.7 min. Recovery of the animals was complete after a total period of 10 to 15 min post-injection. No gross pathomorphological changes were induced when intraperitoneal injections of methohexitone were repeated 10 times within 10 days. In the present study, complete immobilization of the mice was safely achieved after 87 out of 90 injections. In conclusion, immobilization by intraperitoneal injection of methohexitone is a feasible and reliable method in the experimental studies of female mice.     

Therapeutic evaluation of sustained-releasing praziquantel (SRP) for clonorchiasis: phase 1 and 2 clinical studies

Sustained-releasing praziquantel (SRP) tablet was designed for single dose treatment regimen of clonorchiasis. A previous pre-clinical study confirmed its sustained-releasing characteristics and a better cure rate than conventional praziquantel (PZQ). In this clinical study, the pharmacokinetics of this SRP tablet were investigated in human volunteers (phase 1; 12 volunteers), and its curative efficacy was examined in clonorchiasis patients (phase 2; 20 volunteers). In the phase 1 clinical study, blood concentrations of both tablets showed wide individual variation. The AUClast of SRP was 497.9 +/- 519.0 ng * hr/ml (mean +/- SD) and PZQ of 628.6 +/- 695.5 ng * hr/ml, and the AUCinf of SRP was 776.0 +/- 538.5 ng * hr/ml and of PZQ 658.6 +/- 709.9 ng * hr/ml. Cmax values of SRP and PZQ were 90.7 +/- 82.2 ng/ml and 214.9 +/- 251.9 ng/ml, and Tmax values were 3.42 +/- 1.43 hr and 1.96 +/- 1.23 hr, respectively. SRP tablets showed similar AUC values, but lower Cmax and longer Tmax values than PZQ. In the phase 2 study, SRP at 30 mg/kg (single dose) achieved a 60% cure rate and a 95.5% egg reduction rate. The cure rate of a single dose SRP was unsatisfactory compared with that of the conventional PZQ dose, but much better than that achieved by a single dose PZQ.     

Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.     

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.     

Effects of varying doses of methionine sulfoximine on liver glutamine synthetase activity and time courses of blood and urinary nitrogenous compounds in the chicken (Gallus domesticus)

1. The activity of liver glutamine synthetase was inhibited to 7-12% of the control activity by an intracardiac injection with methionine sulfoximine (MSM) at dosages of 20, 50, 75 and 100 mg/kg body wt. 2. Plasma glutamine concentrations in all the MSM treatments decreased sharply, then reached steady-state levels within 0.5-2.5 hr, which were almost proportional to a dose of MSM. 3. Blood ammonia concentration sharply increased to a steady-state level attained at 4.5 hr, which was proportional to a dose of MSM. The excretion rate of urinary ammonia augmented linearly up to the dose dependent maximum rates within 2-5 hr. 4. Plasma uric acid concentration dropped linearly by about 6.4 mg/100 ml at doses of 50, 75 and 100 mg MSM and by 3.7 mg/100 ml at a dose of 20 mg MSM within 2.5 hr, then recovered a little. 5. The decreases in excretion rates of urinary uric acid for the first 4 hr were almost the same at doses of 50 mg and larger, being twice as large as that of the control chicken. 6. Any doses of MSM affected neither the time course of excretion rate of total urinary nitrogen nor its total amounts for 7 hr after MSM treatment.