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Biomedical subjects

C Y Cheung

Publications and source records attributed to C Y Cheung.

At least 73 records · Page 4Linked to original sources
PubMed1989

Adrenal growth and ontogeny of adrenal substance P, enkephalins and catecholamines in the ovine fetus.

Biologically active peptides have been identified in the adrenal glands of several adult mammalian species. Some of these peptides appear to modulate the nicotine-induced catecholamine release from the adrenal medulla. The present study was carried out to investigate the presence and ontogeny of the peptides substance P, met-enkephalin and leu-enkephalin in the ovine fetal adrenal gland from 70 to 140 days gestation (term = 145-150 days). Concurrently, the growth of the fetal adrenal as well as the gestational changes in catecholamine content were determined. The maternal adrenal glands were also studied for comparison. The ovine fetal adrenal gland increased in weight with advancing gestation at a single exponential rate. Total adrenal substance P content correlated with gestational age, while met-enkephalin, leu-enkephalin and total catecholamine contents correlated with adrenal weight. The adrenal content (normalized as per unit protein) of substance P was highest in the young fetuses at 70 days gestation, decreased progressively towards term and, in the adult levels were significantly lower than those measured in the fetuses. The contents of met-enkephalin and leu-enkephalin were low in the young fetuses at 70 days gestation, but reached high levels at 130 to 140 days gestation. Maternal adrenal contents of the two enkephalins were significantly lower than those measured in the near-term fetal adrenal. Total catecholamine content in the fetal adrenal medulla increased as the fetus matured. Norpinephrine was the primary catecholamine present in the medulla of fetuses at 70 and 80 days gestation, while epinephrine was the major one in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1988

Fetal hypoxia elevates plasma atrial natriuretic factor concentration.

Acute hypoxia in the fetus is associated with a reduction in fetal blood volume. We hypothesized that atrial natriuretic factor in the fetal circulation may be one of the factors that mediate this blood volume decrease. Thus the present study was designed to determine the effects of hypoxia on circulating concentrations of atrial natriuretic factor in fetal sheep and correlate these changes with fetal blood volume. Hypoxia was induced in chronically catheterized sheep fetuses by infusing nitrogen containing CO2 into the trachea of the ewe for 30 minutes. Fetal arterial PO2 decreased by 10.2 +/- 1.3 (SE) mm Hg. Plasma atrial natriuretic factor concentration rose concurrently with the fall in PO2 such that atrial natriuretic factor increased to 565 +/- 196 pg/ml from a basal level of 127 +/- 13 pg/ml (p less than 0.001). Fetal blood volume was reduced by 7.2% +/- 2.1% and was significantly related to changes in atrial natriuretic factor levels (p less than 0.0001). At the termination of hypoxia, PO2 returned to normal levels before plasma concentrations of atrial natriuretic factor fell to baseline values. Therefore fetal hypoxia appears to be a potent stimulus for elevating plasma concentration of atrial natriuretic factor in the fetus, and this rise in atrial natriuretic factor in the circulation may be partially responsible for the reduction in fetal blood volume observed during hypoxia.

Animals↗
PubMed1988

Autonomic modulation of fetal atrial natriuretic factor and urine flow responses to vascular volume expansion.

The present study was designed to test the hypothesis that the fetal autonomic nervous system modulates the fetal plasma atrial natriuretic factor and urine flow responses to vascular volume expansion. To do this, isotonic saline solution (2% of estimated body weight) was infused intravascularly over a 10-minute period into autonomically intact or autonomically blocked fetal sheep. The autonomically intact fetuses responded to the infusion with a significant rise in arterial and venous pressures (p less than 0.0001), and atrial natriuretic factor increased by 36 +/- 8 (SE) pg/ml (p less than 0.05). In the autonomically blocked fetuses, the arterial pressure rise was greater (7.5 +/- 1.3 vs 2.6 +/- 0.7 mm Hg), whereas the venous pressure rise was not different from that seen in the intact fetuses. Atrial natriuretic factor increased by 44 +/- 20 pg/ml (p less than 0.05) in the blocked fetuses. Urine flow increased by similar amounts in the two groups (maximal increase above control of 0.33 +/- 0.11 in the intact and 0.27 +/- 0.10 ml/min in the blocked fetuses). Thus autonomic blockade did not significantly alter either the atrial natriuretic factor, urine flow, or venous pressure responses to volume loading in the fetal sheep. Therefore it appears that the autonomic nervous system does not play a major role in modulating atrial natriuretic factor, urine flow, or venous pressure responses to acute vascular volume expansion in the late gestational fetal sheep.

Animals↗
PubMed1988

Norepinephrine effects on fetal cardiovascular and endocrine systems.

Norepinephrine (NE) was infused intravenously into near-term chronically catheterized sheep fetuses for 30 min. Infusions of 0.39, 1.2, 3.9, 12, and 39 micrograms/min caused a 1- to 300-fold increase in plasma NE concentration. Fetal arterial pressure increased in a dose-dependent manner up to a maximum of 72 +/- 5% above basal levels at 6-7 min and gradually declined thereafter. Venous pressure increased during the four highest infusion rates to a maximum at 6-7 min followed by a return toward normal. Fetal blood volume underwent a rapid dose-dependent decrease by a maximum of 12 +/- 1% during 39-micrograms/min infusions of NE. Heart rate initially decreased by up to 40 beats/min during the 3.9-, 12-, and 39-micrograms/min infusions, returned to normal within 10 min, and increased to 50 beats/min above control by the end of the 30-min infusion. Plasma concentrations of arginine vasopressin, epinephrine, and plasma renin activity did not change during or after the four lowest infusion rates. Thus fetal vascular pressures and blood volume are altered in a dose-dependent manner over a broad range of plasma NE concentrations. In addition, NE does not appear to affect other circulating vasoactive hormones within its physiological range of concentrations.

Animals↗
PubMed1988

Fetal and adult urine flow and ANF responses to vascular volume expansion.

Isotonic saline (2% of body wt) warmed to body temperature was infused intravascularly over 10 min into chronically catheterized, near-term fetal sheep and into nonpregnant adult sheep. Although both groups of animals underwent the same initial increase in urine flow rate relative to body weight, the diuresis was significantly more prolonged in the adult compared with the fetus. The adult demonstrated a sustained increase in plasma atrial natriuretic factor (ANF) concentration with a suppression of plasma renin activity (PRA) and plasma arginine vasopressin (AVP). In the fetus, only a transient rise in plasma ANF with no change in PRA or AVP occurred. The increases in blood volume and arterial pressure were significantly greater in the adult compared with the fetus, but the venous pressure changes were the same. Thus it appears that fetal and adult kidneys have the same initial urine flow response to rapid vascular volume loading presumably due to a pressure diuresis and elevations in ANF. The more prolonged diuresis in the adult appears attributable to more extensive and prolonged changes in plasma hormone concentrations. The latter, in turn, may be due to the greater intravascular retention of the infused fluid in the adult than in the fetus.

Animals↗
PubMed1987

Norepinephrine regulation of fetal heart rate: multiple mechanisms of action.

Norepinephrine was infused intravenously for 30 minutes into chronically catheterized sheep fetuses averaging 133 days' gestation. At infusion rates of 3.9, 12, and 39 micrograms/min, heart rate initially decreased as much as 40 bpm and then gradually increased to 50 bpm above the control value by the end of the infusion. Thereafter, heart rate increased further, and by the end of a 30-minute recovery period, heart rate was still 66 bpm above the control value. In fetuses pretreated with either a ganglionic blocker or a parasympathetic blocker, norepinephrine caused a large and sustained rise in heart rate by 124 bpm, which declined rapidly when the infusion was terminated. These results suggest that circulating norepinephrine affects fetal heart rate by several mechanisms: a baroreceptor-mediated suppression, a direct stimulation by norepinephrine, a gradual weakening of the vagal and an increase in cardiac sensitivity to sympathetic stimulation. In addition, there appears to be a long-term positive correlation between fetal heart rate and circulating norepinephrine levels.

Animals↗
PubMed1987

Atrial natriuretic factor in maternal and fetal sheep.

To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration (13 +/- 2 pg/ml) was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney.

Allantois↗
PubMed1987

Role of catecholamines in mediating fetal blood volume decrease during acute hypoxia.

Hypoxia was induced in chronically catheterized sheep fetuses at 133 days gestation (term = 145-150 days) by lowering the O2 content of air inspired by the ewe while supplementing with 1-3% CO2. Control fetal arterial oxygen tension (PO2) averaged 22.5 +/- 0.4 (SE) mmHg. During 30 min of mild hypoxia (PO2 decrease less than 6 mmHg) in normal fetuses, fetoplacental blood volume decreased by 4.7 +/- 0.4% and fetal PO2 by 4.3 +/- 0.7 mmHg. In fetuses with alpha- plus beta-receptor blockade, no change in blood volume occurred during mild hypoxia even though PO2 decreased by 3.4 +/- 0.5 mmHg. During severe hypoxia (PO2 decrease greater than or equal to 6 mmHg), fetal blood volume decreased by 9.2 +/- 1.4% and PO2 by 10.4 +/- 0.4 mmHg in normal fetuses. After adrenergic receptor blockade, blood volume decreased by 7.6 +/- 2.5% when PO2 decreased by 8.0 +/- 0.8 mmHg. Fetal arterial and venous pressure were unchanged during mild hypoxia. Vascular pressures increased significantly during severe hypoxia in normal and blocked fetuses, but these were significantly delayed following adrenergic blockade. Thus, although the catecholamines appear to mediate the decrease in fetal blood volume during mild hypoxia, they appear to have little effect on the blood volume decrease that occurs during severe hypoxia. In addition, the changes in blood volume are not directly correlated with the changes in arterial and venous pressures.

Animals↗
PubMed1987

Cardiovascular and fluid responses to atrial natriuretic factor in sheep fetus.

Presently little is known about the effects of atrial natriuretic factor (ANF) in the fetus. In this study we explored the effects of ANF on vascular pressures and fluid dynamics in the chronically catheterized sheep fetuses averaging 133 days gestation (term = 145-150 days). Under resting conditions plasma ANF concentration was positively correlated with fetal heart rate (P less than 0.001) and was not correlated with arterial pressure, venous pressure, or plasma osmolality. The weight-normalized fetal urine flow rate correlated positively with ANF concentration (P less than 0.01). After a bolus injection of 8 micrograms/kg of synthetic human ANF into the inferior vena cava, fetal arterial pressure decreased by 2 mmHg and remained at this level for 60 min, venous pressure was unchanged, and heart rate increased transiently by 15 beats/min. Urine flow rate increased to 250% of control 5 min after the injection and returned to control at 20 min even though ANF was four times control levels. Fetal blood volume decreased significantly by 5% within 10 min and remained low for 60 min. This decrease in blood volume was greater than the increase in urine flow. A kinetic analysis revealed that ANF disappearance from the plasma could not be adequately characterized with a single rate constant due to exchange between plasma and interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Fetal heart rate, arterial pressure, and blood volume responses to cortisol infusion.

The purpose of this study was to determine whether physiological amounts of cortisol affect the fetal cardiovascular system. Cortisol (4 micrograms/min) or the vehicle was infused intravenously for 5 h into six chronically catheterized sheep fetuses at 127-143 days gestation (term = 145-150 days). In the cortisol-infused animals, plasma cortisol concentration increased from 2.0 +/- 0.6 (SE) to 8.3 +/- 0.9 ng/ml. There was a concomitant decrease in fetal heart rate of 38 beats/min (P less than 1 X 10(-6)) and an increase in arterial pressure. Estimated blood volume decreased by 6% in the cortisol-infused fetuses compared with the vehicle-infused animals (P less than 1 X 10(-4]. In addition, plasma norepinephrine and epinephrine concentrations decreased to 70% of control at the end of the 5-h cortisol infusion, whereas plasma renin concentration decreased to 34% of control. The simultaneous increase in fetal arterial pressure and decrease in estimated blood volume suggest that fetal vascular resistance increased, whereas vascular compliance and/or nonstressed vascular volume decreased. However, this does not appear to be mediated by increases in circulating vasoconstrictor hormone concentrations or increased sympathetic tone. Thus the present study shows that physiological amounts of cortisol have significant effects on the fetal cardiovascular system but the mechanisms are unknown.

Analysis of Variance↗
PubMed1986

Epidermal growth factor stimulates the synthesis of its own receptor in a human breast cancer cell line.

The MDA 468 human breast carcinoma cell line was examined for changes in epidermal growth factor (EGF) receptor synthesis and degradation under the influence of EGF. This cell line was used because it overexpresses the EGF receptor such that each cell has 10(6) receptors, but unlike the well-studied A431 cell, its receptor gene is amplified but is not rearranged. On exposure to EGF, total cellular receptor protein, measured by immunoprecipitation with monoclonal antibody B1D8, is reduced. The half-life of receptor metabolically labeled with L-[35S]methionine is 24 h in the absence of EGF and is reduced to 12 h in the presence of 10(-9) M EGF. To measure the effect of EGF on synthesis of the receptor, pulse labeling conditions were selected in which the rate of synthesis of the receptor precursor were followed. EGF had no significant effect on the rate of general protein synthesis in these cells, yet stimulated the synthesis of the EGF receptor 1.8-fold over the unstimulated rate. This increase in receptor precursor synthesis showed time and dose dependence. Stimulation could be detected after 3 h exposure to EGF with a maximum at 6-8 h. A concentration of 10(-11) M EGF gave detectable stimulation with maximal stimulation occurring at 10(-9) M. Longer times and higher concentrations gave submaximal stimulation. A similar dose-response relationship was observed when the rate of mature 170-kDa receptor protein synthesis was measured. These studies demonstrate that EGF stimulates the synthesis of it own receptor. Downregulation of the receptor by EGF results from an increased rate of receptor degradation and not decreased synthesis.

Antibodies, Monoclonal↗
PubMed1986

Fetal cardiovascular and endocrine responses to prolonged fetal hemorrhage.

Twelve chronically catheterized fetal sheep averaging 131 +/- 1 (SE) days gestation (term = 145-150 days) were hemorrhaged an average of 30.8 +/- 1.8% of their initial blood volume over 2 h by removing blood at 10-min intervals. During the hemorrhage, fetal blood volume decreased by 14.3 +/- 1.4%, and arterial pressure (AP), venous pressure (VP), and heart rate (HR) did not change significantly, although fetal plasma renin activity (PRA), arginine vasopressin (AVP), and norepinephrine (NE) were elevated to 1.5-2.5 times their initial values (P less than 0.05). Circulating levels of PRA, AVP, and NE began to rise when 5-10, 10-15, and 20-30%, respectively, of the initial blood volume was removed. Three to five hours after the hemorrhage, blood volume had returned to normal, AP was reduced by an average of 6 mmHg, VP was unchanged, and HR was elevated by an average of 20 beat/min; PRA, AVP, and NE averaged two to three times control (P less than 0.05). Twenty-two hours after the hemorrhage, blood volume was 5.4 +/- 2.4% above control; AP and HR returned toward normal; VP was elevated by an average of 2 mmHg; PRA and NE levels remained elevated (P less than 0.05), but AVP was not different from control. Plasma concentrations of epinephrine, dopamine, and prolactin showed little change during or after the hemorrhage. Thus these studies indicate that the fetus rapidly returns its blood volume to normal after a substantial loss of blood. In addition, the fetal cardiovascular and endocrine responses to a prolonged fetal hemorrhage of moderate volume are substantially less than those that occur after rapid hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Role of arginine vasopressin in fetal renal response to hypertonicity.

We studied the effects of hyperosmolality on fetal renal function and the role of arginine vasopressin (AVP) in these responses. NaCl (9%) was injected intravenously into chronically catheterized ewes and their fetuses, followed by a continuous infusion of 9% NaCl into the ewes. The fetuses were either normal, infused with AVP, or infused with an AVP antagonist. In normal fetuses NaCl injection caused fetal and maternal blood osmolalities to be elevated by 10-15 mosmol/kg for 4 h with no change in fetal blood volume; fetal plasma AVP rose 42%. Fetal arterial pressures rose transiently by 2-10 mmHg. Fetal urine flow rose transiently by 73% after NaCl injection and then averaged 27% below control after 1 h, whereas fetal urine osmolality increased from 188 +/- 31 to 282 +/- 33 mosmol/kg. In a second group of fetuses AVP infusion alone caused fetal urine osmolality to increase by 123 +/- 39 mosmol/kg and urine flow to fall 31%, whereas in a third group the antagonist alone had no effect on urine flow or osmolality. After hypertonic injection into fetuses infused with AVP or the antagonist, the transient changes were similar to those in normal fetuses. However, the sustained increase in urine osmolality and decrease in flow after hypertonic injection were abolished in AVP-infused and antagonist-infused fetuses. Thus it appears that the transient changes in fetal renal function after hypertonic injection are not AVP-induced and may be due to transient increases in arterial pressure, whereas the prolonged changes in urine flow and osmolality appear to be mediated by increases in fetal plasma AVP levels.

Animals↗
PubMed1986

Catecholamine secretion from the adrenal medulla of the fetus, regulation by hormones.

In the ovine fetus, the adrenal medulla activity secretes catecholamines into the circulation under normal and stress conditions. Little is known regarding the endocrine regulation of adrenal medullary catecholamine secretion in the fetus. The present study was undertaken to investigate the direct effects of the hormones prolactin, angiotensin II and cortisol on catecholamine release from fetal adrenal medulla, and to determine whether the effect of the hormones change during development into adulthood. Adrenal medulla from fetal, newborn and adult pregnant sheep was collected, dispersed into single cells and plated. Following preincubation, the cells were treated with ovine prolactin or angiotensin II at 8, 40 and 200 micrograms/ml; or cortisol at 10(-8), 10(-7) and 10(-6)M for 24 h. Catecholamine release into the medium were measured at 3, 6, 12 and 24 h. Ovine prolactin at 8 to 200 micrograms/ml significantly stimulated the release of total catecholamines after 12 h of incubation. The effect of prolactin was dose-dependent such that the magnitude of the response increased and the response time shortened with increasing concentrations of prolactin. In addition, the release of all three catecholamines--dopamine, norepinephrine and epinephrine--was significantly elevated. In newborn cells, only the highest concentration of 200 micrograms/ml ovine prolactin stimulated total catecholamine release at 6 h and 12 h, with significant increases of the three catecholamines at 12 h. In maternal cells, stimulation of catecholamine release was observed also with the highest concentration of prolactin tested (200 micrograms/ml) and after 12 h of incubation, when only the release of epinephrine was significantly enhanced by 324%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1985

Vasopressin dose-response effects on fetal vascular pressures, heart rate, and blood volume.

To determine the effects of circulating arginine vasopressin (AVP) on fetal arterial pressure, venous pressure, heart rate, and blood volume, we infused graded amounts of AVP into chronically catheterized fetal sheep at 122-136 days gestation (term 145-150 days). Plasma AVP concentrations increased by 6.5 +/- 3.9 (SE), 13.0 +/- 2.4, 55 +/- 11.7, and 144 +/- 42 pg/ml with infusion rates of 1, 3.3, 10, and 33 ng/min, respectively. Fetal arterial pressure rose 0, 7.2 +/- 1.0, 9.1 +/- 2.5, 11.4 +/- 2.9, and 12.1 +/- 2.4 mmHg while heart rate decreased 0, 24 +/- 5, 36 +/- 10, 59 +/- 9, and 62 +/- 9 beats/min during AVP infusions of 0.5, 3.3, 10, 33, and 700 ng/min, respectively. Fetal venous pressure was unchanged except that it increased 2.4 +/- 0.5 and 4.8 +/- 1.5 mmHg at infusion rates of 33 and 700 ng/min, respectively. Fetal blood volume remained unchanged except for a 7.2 +/- 3.4% decrease with 700 ng/min. After blockade of the fetal autonomic nervous system, the arterial pressure increase was twice and the heart rate decrease was one-third of those observed in autonomically intact fetuses with comparable AVP infusion rates. Thus these fetal cardiovascular variables showed differential sensitivity to increases in circulating AVP concentrations, suggesting that physiological variations in endogenous AVP may have short-term effects on fetal arterial pressure and heart rate, but probably not on venous pressure or blood volume.

Animals↗
PubMed1984

Enhancement of adrenomedullary catecholamine release by adrenal cortex in fetus.

Catecholamines (CA) release from ovine fetal adrenomedullary cells was greatly enhanced by coincubation with adrenocortical cells. Total CA release was significantly elevated at 2 and 6 h of preincubation by seven- and twofold, respectively. With continuous coincubation of the two cell types, the enhancement of release was found to occur as early as 30 min and maintained for at least 6 h. A similar enhancement effect was observed when adrenomedullary cells were incubated in adrenocortical cell incubation medium (ACM). The stimulation of release was demonstrated for each of the three CA: dopamine, norepinephrine, and epinephrine. The effect of adrenocortical cells differed from that of adrenal steroids, because cortisol selectively stimulated the release of epinephrine only by one- to threefold after a latency of 6 to 9 h, whereas dehydroepiandrosterone had no effect on the release of the three CA at any time tested. Finally, the CA stimulatory activity in ACM was acid and heat stable, not extractable by ether but inactivated by proteolytic digestion. These results suggest that the adrenal cortex of the near-term ovine fetus secretes a factor that stimulates the release and perhaps synthesis of CA from the adrenal medulla.

Adrenal Cortex↗