摘要:

Transplacental passage of125I-labelled synthetic rat atrial natriuretic peptide (ANP) was investigated in 20-day pregnant rats under pentobarbitone anesthesia. Although significant quantities of radioactivity were detected in the fetal plasma after maternal injections and in the maternal plasma after fetal injections of125I-labelled synthetic ANP, no fraction of the placentally transferred radioactivity was due to intact ANP. Despite a rapid maternal and fetal metabolism of ANP, both maternal and fetal plasma radioactivity remained relatively stable for at least 3 h and less than 10% of the injected radioactivity was excreted in the maternal urine during a 90-min period. It is concluded that ANP is not transported in either direction across the placenta in rats.Key words: atrial natriuretic peptide, placental barrier, urinary excretion, maternal metabolism, fetal metabolism.

ISSN:0008-4212    

DOI:10.1139/y89-001

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

Five wethers were surgically prepared with cranial implants to study the role of gabaminergic neural pathways on the hypothalamic control of feeding behaviour in ruminants. In the first experiment, the animals were injected (1 μL) with a physiological Tyrode (0.95%) solution, muscimol (0.5 and 1.0 nmol), GABA (0.5 and 1.0 nmol), andL-glutamic acid (0.5 and 1.0 nmol). Feed intake following injections of muscimol (1.0 nmol) andL-glutamic acid (0.5 and 1.0 nmol) was twice as large as that following the Tyrode solution, at 60-min postinjections. These results, however, were not statistically significant (p = 0.12–0.15). In the second experiment, the animals were injected (1 μL) with saline, muscimol (0.8 nmol),L-glutamic acid (0.8 nmol), and pentobarbital (0.26 μmol). Fifteen minutes after the injections, pentobarbital had induced a significant feeding response when compared with control values (p < 0.01), whereas the effect ofL-glutamic acid was not significant. However, 30 min after the injections, feed intake of sheep having receivedL-glutamic acid was higher than that obtained with the control injections (p < 0.01). The response to pentobarbital was stronger than that to either muscimol orL-glutamic acid. Histological analyses of brain tissue indicated that injections were performed in the ventromedial hypothalamus of four sheep and in the dorsomedial hypothalamus of the other. The data indicate thatL-glutamic acid stimulates feed intake by acting either as a precursor of GABA or by a direct stimulation of glutaminergic neural pathways involved in the control of feed intake.Key words: Feeding behaviour, glutamic acid, GABA, sheep.

ISSN:0008-4212    

DOI:10.1139/y89-002

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

The purposes of this study were to examine (a) the effects of acute exercise on metabolic rate 24 and 48 h postexercise and (b) the interaction of acute exercise and the thermic effect of caffeine on metabolic rate and hormonal changes during the late postexercise recovery period. In six young males, who were regular consumers of caffeine, resting energy expenditure was measured before and after caffeine (5 mg∙kg−1) and placebo ingestion under the following conditions: (i) control (e.g., no prior exercise), (ii) 24 h postexercise, and (iii) 48 h postexercise. Blood samples were drawn for plasma glucose, insulin, glycerol, free fatty acids, catecholamines, and thyroid hormones (triiodothyronine, thyroxine, and free thyroxine). Results showed that acute exercise did not exert a detectable effect on resting metabolic rate in the late postexercise recovery period, that is, resting metabolic rate was similar among the conditions of control (1.17 ± 0.12 kcal∙min−1), 24 h postexercise (1.16 ± 0.12), and 48 h postexercise (1.16 ± 0.11). Caffeine ingestion increased metabolic rate (~7%), but the thermic effect was not different among the experimental conditions. Plasma insulin and norepinephrine were lower after caffeine ingestion, whereas an increase in plasma free fatty acids was noted. Other hormones and substrates did not change significantly in response to caffeine ingestion. Furthermore, the hormonal and substrate milieu was not significantly different 24 and 48 h postexercise when compared with the control condition. Our results support the view that acute exercise does not alter the resting metabolic rate in the late postexercise recovery period. Moreover, acute exercise does not potentiate the thermic effect of caffeine in the late postexercise recovery in caffeine-tolerant males.Key words: caffeine, resting metabolic rate, acute exercise, hormones, substra

ISSN:0008-4212    

DOI:10.1139/y89-003

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4binding in guinea pig (Kivalue, 0.22 nM) and human (Kivalue, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4binding (IC50value in guinea pig lung, 23 μM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4(respective pA2values, 9.4 and 10.5) and LTE4(respective pA2values, 9.1 and 10.4) and contractions of human trachea induced by LTD4(pA2value, 8.5). L-660,711 (5.8 × 10−8 M) antagonized contractions of guinea pig trachea induced by LTC4in the absence (dose ratio = 28) but not in the presence of 45 mML-serine borate (dose ratio <2). L-660,711 (1.9 × 10−5 M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2α, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 × 10−5 M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4(0.2–12.8 μg/kg) -induced bronchoconstriction in guinea pigs, and p. o. L-660,711 blocked LTD4- andAscaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4and LTE4in asthma and other pathophysiologic conditions.

ISSN:0008-4212    

DOI:10.1139/y89-004

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The presentin vivoelectrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, andN-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate andN-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.Key words: domoate, kainate, excitotoxin, hippocampus,N-methyl-D-aspartate.

ISSN:0008-4212    

DOI:10.1139/y89-005

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

The occluded canine tail artery, which comes off in the same plane as the aortoiliac junction, has been used as a flow model for cerebral aneurysms. These experiments were designed to determine if it is a realistic distensible model of human intracranial aneurysms. Distensibility studies were done on the aorta, and the iliac and tail arteries of four dogs. From these pressure–volume studies, tension–strain curves, elastances, and collagen slack were obtained. The tail artery is stiffer longitudinally and more distensible circumferentially than the other vessels. The iliac arteries and the aorta are not significantly different. The elastance of elastin and collagen is lower in the tail artery, and the collagen is more wavy circumferentially. Longitudinally, the collagen slack is least for the tail artery, and the elastance of elastin is not different in all three vessels. The number of elastin layers in the iliac and tail arteries seen in cross section is not significantly different, but the aorta is different from both these vessels. In another four dogs the aorta proximal to the trifurcation was cannulated and infused with saline to increase pressure. India ink marks were put on the surface to measure changes in length. Photographs were taken at intervals of 10 mmHg(1 mmHg = 133.3 Pa). This was done with the vessels tethered and untethered in the body and then taken out and studied with the same methodin vitro. Arteries tethered in the body expanded circumferentially more than longitudinally. The tail artery becomes less distensible if untethered in the body and therefore acts more like an aneurysm. This makes it a good distensible flow model for aneurysm study. Even though the walls of the tail artery are thick and the geometry is not spherical, it is a reasonable model to study flow in aneurysms.Key words: elasticity, aorta, aneurysm, tethering, canine.

ISSN:0008-4212    

DOI:10.1139/y89-006

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

Cardiac hypertrophy was induced in adult female Wistar rats following 12 days of daily subcutaneous injections of isoproterenol (ISO). The left atria responded with a 13–14% increase in tissue growth, while the ventricles achieved a 34–39% increased tissue mass. Maximum force generation and twitch characteristics in 1.0 mM external Ca2+for the left atria or the right papillary muscle were unchanged in the ISO-treated animals. The force–interval relation was determined at 26 °C between 0.5 and 120 s. The development of maximum force clearly passed through two phases identified as alpha and beta. To characterize these two processes the data were fitted to a two-term linear combination of exponentials (two-compartment model). The time constant and capacity of each process to contribute to the whole force–interval curve was determined by a four-parameter least square fit method. In control atrial muscle the time constants for the alpha and beta processes were 0.47 and 11.23 s, respectively. The contribution of each process to the total force curve in control atrial muscle was approximately 50% alpha and 50% beta. Following ISO-induced growth the time constants were 0.38 and 13.33 s with a shift of contributions towards 60% alpha and 40% beta. Control papillary muscle from the right ventricle had a similar alpha time constant of 0.49 s compared with atrial muscle but possessed a considerably slower beta time constant of 26.17 s. The contribution of each process to interval-dependent force development was 44.5 and 55.5%, respectively. Treatment with ISO to induce ventricular growth resulted in a 20% reduced alpha time constant, with a 45% increased contribution by the alpha process. These results suggest that during the development of catecholamine-induced hypertrophy, there is a significant change in the fundamental alpha process which appears to be mediated by a reduced time constant and an enhanced capacity to contribute to force development.Key words: excitation–contraction, interval-dependent force recovery, post-rest contractions, cardiac muscle, sarcoplasmic reticulum.

ISSN:0008-4212    

DOI:10.1139/y89-007

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

The inhibitory effect of serotonin, released iontophoretically, on acetylcholine-induced facilitation of population spikes evoked by fimbria–commissural stimulation was studied in the CA1 region of rat hippocampusin vivo. After serotonin was applied for 2.6 ± 0.8 min, acetylcholine's action was inhibited in 39 cases out of 57 (68.4%), by 68.9 ± 23.1%, irrespective of whether serotonin alone increased or reduced the population spike. Spiperone, used as a 5-hydroxytryptamine1A(5-HT1A) antagonist, suppressed the inhibitory action of serotonin in 14 of 21 tests. Serotonin had similar effects on population spike facilitations induced by acetyl-β-methylcholine and dimethylphenylpiperazinium. Thus serotonin, probably acting on 5-HT1Areceptors, blocks effectively but indiscriminately all cholinergic facilitations, whether mediated by nicotinic or muscarinic receptors.Key words: serotonin, cholinergic facilitation, hippocampal pyramidal cells, spiperone, muscarinic and nicotinic actions.

ISSN:0008-4212    

DOI:10.1139/y89-008

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

Guanosine diphosphate binding to the uncoupling protein of isolated mitochondria of brown adipose tissue in newborn rabbits was measured as an index of thermogenic activity. The binding was 0.281 ± 0.022 nmol GDP/mg mitochondrial protein at 1 day of age, 0.214 ± 0.017 at 3 days, 0.428 ± 0.038 at 5 days, and 0.208 ± 0.016 at 7 days. The increase in binding between 3 and 7 days of age suggests that the brown fat has an increased thermogenic capacity at that age. In addition, the potential for synthesis of the uncoupling protein was investigated in 1- to 5-day-old newborn rabbits by probing the total cellular ribonucleic acid for the messenger that codes for uncoupling protein. The amount of uncoupling protein messenger was highest at 1 day of age and declined at least until 5 days of age. Because the amount of uncoupling protein messenger decreased as the GDP binding increased, the results suggest that either the initially translated uncoupling protein was unmasked at about 5 days of age or there was a delay in the incorporation of uncoupling protein into the mitochondrial inner membrane, or both.Key words: brown fat, neonatal rabbit, thermogenin, messenger RNA, age-related changes.

ISSN:0008-4212    

DOI:10.1139/y89-009

出版商:NRC Research Press    

年代:1989

数据来源: NRC

摘要:

Venous occlusion of the left arm in consenting men was induced for 10 or 20 min to stimulate local fibrinolytic and other proteases, thereby favouring the conversion of prorenin to renin. Using the two techniques cryoactivation and tryptic activation, we found that plasma active renin increased significantly after such occlusion (10 and 20 min) while prorenin rose more convincingly and progressively from 10 to 20 min. The renin increase can be partially attributed to hemoconcentration, butin vivoproduction and (or) local activation of prorenin to renin cannot be excluded. The prorenin rise can apparently be attributed to local extrarenal production, and not to hemoconcentration or influx, since it was progressive and neither prorenin nor renin levels were raised at all in blood circulating outside the occluded arm. Prekallikrein and plasminogen levels were elevated in occlusion plasmas, but responsibility of these enzyme systems for any enhanced activation of prorenin was not established. The trypsin inhibitory capacity was also elevated, increasing the requirement of trypsin to achieve optimal activation of prorenin, but not changing the prorenin estimate itself. Thus, prorenin appears to be released extrarenally, within the vasculature of an occluded arm, whilein vitroevidence suggests that the mechanisms for its activation were stimulated. The importance of such extrarenal production and activation of prorenin for renin production under other physiological or pathophysiological conditions remains to be determined.Key words: venous occlusion, extrarenal prorenin, production, activation.

ISSN:0008-4212    

DOI:10.1139/y89-010

出版商:NRC Research Press    

年代:1989

数据来源: NRC