Biomedical subjects

J C Rose

Publications and source records attributed to J C Rose.

At least 19 recordsLinked to original sources

PubMed1992

Corticotropin and cortisol responses to corticotropin-releasing factor in the chronically hypoxemic ovine fetus.

OBJECTIVE: The purpose of this study was to determine if mild hypoxemia (approximately 25% below normal) of at least 5 days' duration alters corticotropin and cortisol responses to corticotropin-releasing factor. STUDY DESIGN: We studied 14 (hypoxemic, n = 5; normoxemic, n = 9) fetuses of 135 +/- 1 (mean +/- SEM) days' gestational age. Fetuses were placed in the experimental group if arterial PO2 was < or = 16 mm Hg for 5 days. In normoxemic animals arterial PO2 was > or = 17 mm Hg. Plasma hormone responses were compared by analysis of variance. RESULTS: Resting corticotropin levels were not different (hypoxemic 26 +/- 5 pg/ml, normoxemic 29 +/- 12 pg/ml), and corticotropin-releasing factor (530 +/- 30 ng/kg) increased (p = 0.01) corticotropin levels similarly in both groups. Basal plasma cortisol levels (hypoxemic 20 +/- 10 ng/ml, normoxemic, 30 +/- 7 ng/ml) were not significantly different. Both groups had similarly increased (p < 0.01) plasma cortisol levels after corticotropin-releasing factor administration. CONCLUSION: Mild hypoxemia lasting 5 days does not significantly alter corticotropin and cortisol responses to corticotropin-releasing factor in the late-gestation ovine fetus.

Adrenocorticotropic Hormone↗

PubMed1992

Atrial natriuretic factor concentrations during pregnancy and in the postpartum period.

Atrial natriuretic factor (ANF) is a hormone that regulates fluid and electrolyte homeostasis. Increased intra-atrial pressure or atrial distention, which might occur secondary to intravascular volume expansion, stimulate the secretion of ANF by human atrial myocytes. During normal human pregnancy, there is a progressive increase in total intravascular fluid volume. Thus, we asked the following question: Does this physiologic adaptation to pregnancy result in an increase in ANF concentrations? Concentrations of alpha-human ANF (alpha-hANF) were measured by a specific radioimmunoassay in venous blood samples obtained longitudinally in the first, second, and third trimesters of pregnancy, during the intrapartum period, in the early postpartum period, and 6 to 8 weeks postpartum from 11 normal women who had no antepartum, intrapartum, or postpartum complications. Maternal circulating alpha-hANF levels were not different from those seen in the nonpregnant state. However, higher alpha-hANF concentrations were noted in the early postpartum period. Although the hypervolemia of normal pregnancy is not associated with higher alpha-hANF concentrations, other possibilities (such as increased ANF clearance, dilutional effects) need to be investigated. Finally, the etiology for the transient increase in alpha-hANF levels in the early postpartum period remains to be elucidated.

Adult↗

PubMed1992

ACTH and cortisol responses to sequential CRF injections in fetal sheep.

To determine whether an initial ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to a second injection and to establish whether the effect changes throughout gestation, we studied chronically cannulated fetal lambs of 103-113 and 133-137 days gestation. Experimental groups underwent an injection (500 ng/kg iv) of oCRF, arterial blood sampling for 6 h, then a similar oCRF injection followed by sampling. In control studies, vehicle was the initial injection. After the first oCRF injection, plasma cortisol levels went from 1.7 +/- 0.4 to 9.5 +/- 5.2 (SE) ng/ml ("immature") and from 22.3 +/- 4.9 to 52.5 +/- 5.8 ng/ml ("mature"), remaining elevated for 6 h. In immature fetuses, the first oCRF injection did not alter the ACTH response to a second injection. Cortisol increases were reduced. In mature animals, ACTH and cortisol response to oCRF were eliminated by prior oCRF. Thus a large increase in cortisol after oCRF in mature fetuses is associated with inhibition of the ACTH response to a second oCRF injection, whereas in immature animals a small increase in cortisol after the first oCRF injection is not.

Adrenal Cortex↗

PubMed1992

ACTH and cortisol responses to hypotension in fetal sheep after a prior CRF injection.

To determine whether an ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to hypotension and whether the effect of any interactions between these stimuli changes across gestation, we studied chronically cannulated fetal lambs of 103-113 ("immature") and 133-139 days gestation ("mature"). Experimental groups received 500 ng/kg oCRF injections and 6 h later had arterial pressure reduced 20% for 10 min with nitroprusside. Blood samples were obtained before and after each manipulation. Controls received vehicle instead of oCRF. The oCRF increased plasma cortisol levels from 2.1 +/- 0.4 to 14.2 +/- 4.7 (SE) ng/ml in immature and 44.9 +/- 2.2 to 102.8 +/- 15 ng/ml in mature animals. In mature fetuses the oCRF did not alter plasma ACTH and cortisol increases due to hypotension. In immature animals ACTH increases were normal but cortisol increases were eliminated. This suggests that the CRF caused maximal stimulation of the adrenal gland. In older fetuses, it appears that the action of ACTH-releasing factors, secreted in response to arterial hypotension, can overcome the negative feedback effects of elevations in endogenous cortisol.

Adrenal Cortex↗

PubMed1992

Alterations in oxytocin prohormone processing during early development in the fetal sheep.

Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma.

Animals↗

PubMed1992

Cortisol effect on atrial natriuretic factor response to hypertonic saline in fetal sheep.

Atrial natriuretic factor (ANF) is released following a variety of stimuli including hypertonicity in the fetus. To study the effect that cortisol has on fetal ANF release, seven chronically instrumented fetal sheep at gestational ages ranging from 110-132 days were studied in two experiments. In one experiment (CORTISOL), a continuous cortisol (with EtOH vehicle) infusion was maintained. In the other experiment (CONTROL), the vehicle was infused alone. Ninety minutes from the start of this infusion, a hypertonic saline bolus (12 meg/kg) was given. Osmolality, ANF, cortisol, pH, PO2, PCO2, mean arterial pressure (MAP), heart rate (HR), and hematocrit (HCT) were followed over a 120-min period. Following hypertonic saline, serum osmolality increased from 290.6 +/- 2.3 mOsm/kg to 310.4 +/- 2.5 mOsm/kg (P < 0.01). Baseline values for pH, PO2, and HCT were 7.37 +/- 0.01, 22.5 +/- 1.6 mmHg, and 33.9 +/- 1.2 respectively. Each of these variables fell following hypertonic saline infusion. MAP rose from 40.6 +/- 1.7 mmHg to 47.0 +/- 2.4 mmHg (P < 0.01). However, there were no differences between CONTROL and CORTISOL experiments in any of the above changes. Cortisol levels in the CONTROL group did not change during the course of the experiment, but in the CORTISOL group rose from 8.2 +/- 4.4 ng/ml to 33.0 +/- 9.9 ng/ml (P = 0.02). Plasma ANF levels prior to hypertonic saline were similar (124.8 +/- 17.7 pg/ml and 127.6 +/- 26.1 pg/ml) in the CONTROL and CORTISOL groups respectively and rose following hypertonic saline to a maximum of 155.3 +/- 16.6 pg/ml and 189.2 +/- 42.7 pg/ml (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The ratio of plasma bioactive to immunoreactive ACTH-like activity increases with gestational age in the fetal lamb.

The fetal ovine pituitary-adrenal axis plays an important role in the timing of parturition, in fetal lung maturation, and in fetal and neonatal responses to stress. While the ovine pituitary during the last third of gestation (term = 145 days) is capable of secreting immunoreactive ACTH (iACTH) in response to various stimuli, plasma cortisol levels frequently do not reflect the rise in plasma ACTH. Therefore, we examined the relationship between plasma iACTH and steroidogenic ACTH-like activity (bACTH) in a group of immature fetal lambs (Group I: gestational age = 97 +/- 2 days, mean +/- SEM, n = 16) and a group of near-term fetuses (Group II: gestational age = 136 +/- 1 days, n = 13) following acute exteriorization. Plasma iACTH was determined by RIA. Plasma bACTH was determined by the ability of glass-extracted material to stimulate corticosterone (B) production in an acutely dispersed rat adrenal bioassay. Plasma iACTH and bACTH levels varied among animals within age groups, with iACTH tending to be higher in immature fetal lambs (Group I) than near-term lambs (Group II) and bACTH being higher (P < 0.05) near term than earlier (Group I: iACTH = 807 +/- 273 pg/ml, bACTH = 173 +/- 44 pg/ml; Group II: iACTH = 405 +/- 85 pg/ml, bACTH = 371 +/- 96 pg/ml). The proportion of iACTH that had biologic activity (e.g. B/I ratio) was significantly greater in the older than in the younger fetuses (Group II: B/I = 0.862 +/- 0.109; Group I: B/I = 0.462 +/- 0.105 P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1991

Atrial natriuretic factor responses to volume expansion in pregnant and nonpregnant sheep.

Isotonic volume expansion results in atrial natriuretic factor release by cardiac myocytes. Because pregnancy produces well-established alterations in fluid homeostasis and cardiovascular function, changes in atrial natriuretic factor responses may also occur. This study compares plasma atrial natriuretic factor responses to short-term volume expansion in pregnant and nonpregnant sheep. Seven pregnant and six nonpregnant ewes were chronically instrumented and subjected to a series of four experiments consisting of a control group (no infusion) and groups that received 10 ml/kg, 25 ml/kg, and 40 ml/kg isotonic saline infusion over a 30-minute period. The order of the experiments was random and separated by greater than or equal to 48 hours. Plasma atrial natriuretic factor, osmolality, right atrial pressure, blood pressure, and urine flow were measured over a 150-minute observation period. After volume expansion, plasma atrial natriuretic factor levels rose significantly from 39 +/- 4 pg/ml (mean +/- SEM) to 49 +/- 7 pg/ml, 36 +/- 4 pg/ml to 62 +/- 19 pg/ml, and 39 +/- 6 pg/ml to 67 +/- 14 pg/ml in the nonpregnant group 10 ml/kg, 25 ml/kg, and 40 ml/kg experiments, respectively. In the pregnant groups, plasma atrial natriuretic factor levels rose from 50 +/- 2 pg/ml to 75 +/- 20 pg/ml, 43 +/- 5 pg/ml to 57 +/- 5 pg/ml, and 46 +/- 4 pg/ml to 67 +/- 7 pg/ml, respectively. Differences in atrial natriuretic factor responses were not seen between pregnant and nonpregnant groups at any volume expansion level. As expected, atrial pressure and urine flow significantly increased after all volume expansion experiments. Pregnant and nonpregnant groups were similar with respect to atrial pressure and urine flow responses. Over various volume expansion levels significant associations were seen between atrial pressure, atrial natriuretic factor, and urine flow. These relationships were unaltered by pregnancy. In summary, atrial natriuretic factor responses to volume expansion do not appear to differ between pregnant and nonpregnant sheep.

Animals↗

PubMed1991

Age-dependent differences in active and inactive renin in the lamb fetus.

Most studies examining the developmental aspects of renin secretion in fetal lambs have focused on measurements of active renin. Data from these studies demonstrated age-dependent differences in renin release in vivo and in vitro. However, little information is available concerning gestational changes in total (active and inactive) renin. Therefore, we have measured the renin concentration in plasma, amniotic fluid and various tissues before and after trypsin treatment (for total renin) using 7 fetuses at 0.61-0.79 gestation (immature) and 7 fetuses at 0.88-0.97 gestation (mature). We found that active and total renin levels in plasma and kidney tissues were significantly lower in immature than in mature fetuses, while inactive renin levels were not different. We also found that the amniotic fluid, the adrenal gland, the placenta and membranes all contained low levels of active and total renin that were not different between groups. These results suggest that, over the last third of gestation, maturation influences the regulation of active renin in the kidney and plasma. The data also indicate that the renin concentration in the amniotic fluid, the adrenals, the placenta and membranes is regulated differently than that in the plasma and the kidney.

Adrenal Glands↗

PubMed1990

Interrelationship between atrial natriuretic factor concentrations and acute volume expansion in pregnant and nonpregnant women.

The secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention. To determine whether acute intravascular volume expansion affects atrial natriuretic factor concentrations during pregnancy, circulating atrial natriuretic factor levels were measured in pregnant women at term (before elective cesarean section) and nonpregnant control subjects before and during intravenous infusion of lactated Ringer's solution (approximately 30 ml/kg). Venous plasma concentrations of alpha-human atrial natriuretic factor were determined by a specific radioimmunoassay. A significant increase in alpha-human atrial natriuretic factor levels in nonpregnant subjects was seen. Pregnant women did not show a significant response to a similar stimulus. Finally, basal alpha-human atrial natriuretic factor levels in pregnant and nonpregnant women were not different. Volume expansion (long-term or short-term) in normal human pregnancy may not be sensed by atrial volume sensors, possibly because it is accommodated by an enlarged maternal vascular compartment.

Atrial Natriuretic Factor↗

PubMed1990

The effect of adrenocorticotropic hormone infusion on subsequent pituitary response in the sheep fetus.

It is not known whether activation of the fetal adrenal gland can inhibit pituitary adrenal responses to stress. Therefore we treated 14 chronically cannulated sheep fetuses (gestational age range, 109 to 129 days) with an adrenocorticotropic hormone infusion of 5 ng/kg per minute or vehicle solution at similar rates for 2.5 hours and then subjected them to a 10-minute period of hypotension. Resting mean arterial blood pressures were similar for both control and adrenocorticotropic hormone infusion groups and decreased similarly after administration of sodium nitroprusside. Resting fetal plasma cortisol levels (11.6 +/- 3.3 ng/ml) and adrenocorticotropic hormone (42 +/- 15 pg/ml) concentrations were not different in the two groups. In the control group fetal plasma cortisol concentrations rose from 12.1 +/- 1.7 to 35.7 +/- 8.0 ng/ml after hypotension (p less than 0.05) and plasma adrenocorticotropic hormone increased from 37 +/- 19 to 145 +/- 67 pg/ml (p less than 0.05). In the group treated with adrenocorticotropic hormone, fetal plasma cortisol concentrations increased (30.2 +/- 7.8 to 53.6 +/- 15.0 ng/ml; p less than 0.05) after hypotension whereas fetal plasma adrenocorticotropic hormone concentrations did not increase (398 +/- 227 versus 258 +/- 77 pg/ml; p greater than 0.05).

Adrenocorticotropic Hormone↗

PubMed1990

Renin secretion by fetal lamb kidneys in vitro.

We studied the content and secretion of renin by renal cortical slices obtained from ovine fetuses at 0.62-0.77 gestation (n = 5 immature) and at 0.84-1.00 gestation (n = 5 mature). Renin content of fresh slices and renin secretion after the incubation of slices in Robinson's medium with or without isoproterenol or dibutyryl (DB) adenosine 3',5'-cyclic monophosphate (cAMP) (10(-4)-10(-8) M) were measured. Renin content of immature fetal kidneys (ng.ml homogenate-1.h-1.mg-1) and basal renin secretion rate [ng (ANG I/h).mg tissue-1.h incubation-1] were 24.3 +/- 3.0 and 1.4 +/- 0.4, respectively. Both of these values were significantly lower (P less than 0.02) than the corresponding results obtained with mature fetal kidneys (67.0 +/- 4.5 and 3.4 +/- 0.5). Renin content and basal secretion rates were strongly correlated (r = 0.78, P less than 0.01). The addition of isoproterenol or DBcAMP induced a significant increase in renin secretion only when incubated with slices from mature fetuses. We conclude that there is a deficit in the beta-adrenoceptor-mediated renin release distal to cAMP formation in immature fetuses, which may be related to low renal content of renin at this stage of development.

Analysis of Variance↗

PubMed1990

Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity.

We measured the concentration of progesterone and estradiol and calculated the progesterone:estradiol ratio in nonpregnant and pregnant human myometrium. Progesterone, estradiol and the progesterone:estradiol ratio were higher in pregnant than in nonpregnant myometrium. There was no difference in the concentration in the presence of labor. The progesterone:estradiol ratio showed a similar pattern. We also investigated the effect of the ovarian steroids on the activity of cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE). Progesterone in pharmacologic doses inhibited the activity of the high-affinity enzyme as much as 72% and the low-affinity form as much as 34%. High-affinity phosphodiesterase from nonpregnant myometrium was the least sensitive to inhibition, and the enzyme from pregnant myometrium obtained from laboring women was the most sensitive. Low-affinity phosphodiesterase from nonpregnant myometrium was less sensitive to inhibition than enzyme from pregnant women with or without labor. The degree of inhibition of the low-affinity enzyme in the two pregnant groups was not different. The type of inhibition was competitive in both the high- and low-affinity forms. Estradiol at similar concentrations did not have any effect on the activity of the enzyme. Progesterone in part may exert its effect on the human myometrium by its effect on cyclic adenosine monophosphate-PDE activity and the metabolism of cAMP.

Adenosine Monophosphate↗

PubMed1989

Atrial natriuretic factor maternal and fetal concentrations in severe preeclampsia.

There is a reduction in intravascular volume in patients with preeclampsia. Since the secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention, we sought to determine whether circulating maternal plasma atrial natriuretic factor concentrations were lower in patients with preeclampsia compared to normal pregnant women. The level of alpha-human atrial natriuretic factor was measured by a specific radioimmunoassay. Maternal venous concentrations of a alpha-human atrial natriuretic factor were higher in patients with severe preeclampsia (116.12 +/- 13.37 pg/ml) than in normal pregnant women (80.30 +/- 4.02 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher in fetuses born to patients with severe preeclampsia (197.68 +/- 29.10 pg/ml) than normal control subjects (118.00 +/- 12.52 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher than umbilical or maternal venous concentrations. In cases of severe preeclampsia, despite the presumed volume changes, maternal atrial natriuretic factor concentrations are higher than in normal pregnant women. The fetus appears to produce its own atrial natriuretic factor. Umbilical artery atrial natriuretic factor concentrations in fetuses born to preeclamptic mothers are higher than those seen in normal control subjects.

Adolescent↗

PubMed1989

Blood volume restitution after hemorrhage in the newborn lamb.

Blood volume restitution after hemorrhage was investigated in lambs in the first week of life. Two groups of nonsplenectomized lambs were bled 10 and 20% of their blood volume at 2%/min while being suspended horizontally in a sling with their legs dependent, and a third group was bled 20% while lying down. Blood pressure fell 8% in the lambs bled both 10 and 20% while lying down and 44% in those bled 20% while being suspended. Blood volume was completely restored in all three groups by 5 h after the hemorrhage, the rate of restitution being equal among the groups. The initial phase of restitution was slower when the lambs were bled while lying down. Vasopressin levels were increased only in the lambs bled 20% of their blood volume while being suspended. Plasma renin activity increased similarly in all groups. Hemorrhage increased plasma glucose but did not change plasma protein and serum osmolality. We conclude that lambs bled up to 20% of blood volume restitute relatively quickly at a rate independent of the volume shed. The position of the animal affects the degree of hypotension, the levels of vasopressin, and the rate of the initial phase of volume restoration.

Animals↗

PubMed1989

Effect of cortisol on vasopressin response to hypertonic saline in fetal sheep.

To determine the effect of cortisol on vasopressin responses to hyperosmolality, we infused hypertonic saline (HS) (12 meq/kg NaCl) into nine chronically cannulated fetal sheep ranging from 110 to 132 days of gestation. The experiment was performed twice on each fetus, once during a continuous cortisol infusion and once during a vehicle infusion. Administration of HS resulted in a prompt increase in serum osmolality from 292.1 +/- 1.8 to 310.4 +/- 2.5 mosmol/kg. Decreases were seen in pH, partial pressure of O2, and hematocrit from 7.37 +/- 0.01 to 7.31 +/- 0.01, from 22.5 +/- 1.6 to 20.0 +/- 2.0 mmHg, and from 35.6 +/- 1.7 to 32.6 +/- 1.6, respectively. Mean arterial pressure increased from 41.3 +/- 1.4 to 48.9 +/- 2.0 mmHg (P less than 0.01). Arginine vasopressin (AVP) rose from base line after HS (P = 0.11 vehicle experiments, P = 0.04 cortisol experiments), and AVP responses were greater in the cortisol experiments than in the vehicle experiments (delta AVP = 21.9 +/- 10.9 vs. 3.1 +/- 0.9 pg/ml, P = 0.05). Also there was a correlation noted between differences in AVP response and cortisol levels (P less than 0.04). We conclude that cortisol exerts a positive influence on the AVP response to HS in fetal sheep.

Animals↗

PubMed1989

Comparison of high-dose opioid antagonist effects on ovine fetal cardiovascular function.

The opioid antagonists, naloxone (NOX) and naltrexone (NTX), were found to produce dose-dependent increases in fetal mean arterial pressure over a dose range of 5-80 mg/kg. There was a concomitant decrease in fetal heart rate up to 40 mg/kg. Above this dose, NOX and NTX caused an increase in heart rate as well as blood pressure. NTX produced similar effects in maternal ewes, although at lower doses (mg/kg) than those needed for fetal lambs. There were no age-related differences in antagonist effects in two fetal age groups studied (100-116 and 124-144 days of gestation). The partial antagonist, levallorphan (LVL), produced effects which were qualitatively similar to those produced by NOX and NTX in doses up to 20 mg/kg. These effects were not stereospecific, as the enantiomer of LVL, dextrallorphan, produced similar effects at equal doses. Pretreatment with the alpha 1-adrenoreceptor antagonist, prazosin, abolished the opioid antagonist effects on fetal blood pressure. We postulate that high doses of opioid antagonists activate sympathetic systems to increase fetal blood pressure through mechanisms which do not involve interactions with mu, delta or kappa opioid receptors.

Animals↗

PubMed1988

Arginine vasopressin infusion stimulates adrenocorticotropic hormone and cortisol release in the ovine fetus.

Arginine vasopressin may play a role in the control of adrenocorticotropic hormone release during stress in the adult animal. Arginine vasopressin is also considered an important stress hormone in the fetus. The effect of arginine vasopressin infusion on adrenocorticotropic hormone release in the fetus was investigated in 14 chronically cannulated ovine fetuses with normal blood gas and pH values between 103 and 137 days' gestation. There was a significant increase in adrenocorticotropic hormone and cortisol levels during a 30-minute infusion of arginine vasopressin. Plasma renin activity was unchanged. The corticotropin-releasing activity of arginine vasopressin was not blocked by pretreatment with a V1-receptor antagonist and was not significantly different when the pressor response was attenuated by sodium nitroprusside infusion.

Adrenocorticotropic Hormone↗