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Biomedical subjects

W M Barron

Publications and source records attributed to W M Barron.

At least 37 records · Page 2Linked to original sources

Changes in the metabolic clearance of vasopressin and in plasma vasopressinase throughout human pregnancy.

Metabolic clearance rates (MCR) of arginine vasopressin (AVP) were measured serially in five women starting before conception, during gestational weeks 7-8 (early), 22-24 (middle), and 36-38 (late pregnancy), and again 10-12 wk postpartum. Hormonal disposal rates were determined after water loading to suppress endogenous AVP release using a constant infusion method designed to achieve three different steady-state concentrations of plasma AVP (PAVP) on each test occasion. Dose schedules were altered in mid- and late pregnancy to obtain comparable AVP levels at each stage of the protocol. Prehydration decreased plasma osmolality sufficiently to suppress AVP release, as circulating AVP-neurophysin measured serially in three of the women was undetectable. The MCR of AVP was similar before conception (0.75 +/- 0.31, 0.79 +/- 0.34, and 0.76 +/- 0.28 liters/min at PAVP of 2.6 +/- 1.9, 4.7 +/- 2.4, and 8.3 +/- 3.9 pg/ml), in early pregnancy (0.89 +/- 0.34, 0.97 +/- 0.04, and 0.95 +/- 0.40 liters/min at PAVP of 2.2 +/- 2.1, 3.9 +/- 3.2, and 7.9 +/- 3.4 pg/ml), and postpartum (0.70 +/- 0.21, 0.69 +/- 0.24, and 0.75 +/- 0.20 liters/min at PAVP 3.5 +/- 1.8, 5.1 +/- 3.7, and 9.1 +/- 4.2 pg/ml). Values at mid-pregnancy (2.8 +/- 1.3, 3.0 +/- 1.2, and 2.7 +/- 1.2 liters/min at PAVP 2.3 +/- 2.2, 4.0 +/- 3.6, and 7.7 +/- 3.9 pg/ml) and late pregnancy (3.2 +/- 1.4, 3.3 +/- 1.4, and 2.9 +/- 1.2 liters/min at PAVP 1.9 +/- 2.0, 3.8 +/- 2.6, and 7.4 +/- 4.1 pg/ml) increased 3-4-fold (all P less than 0.01). Plasma vasopressinase, undetectable at 7-8 gestational wk, increased markedly by mid- and slightly more by late gestation. Finally, relationships between PAVP and urine osmolality were similar before, during, and after pregnancy. We conclude that marked increments in the MCR of AVP occur between gestational weeks 7 and 8 and mid-pregnancy, which parallel the period of greatest rise in both trophoblastic mass and plasma vasopressinase. There was no evidence of a renal resistance to AVP during gestation.

Aminopeptidases↗

Recurrent diabetes insipidus associated with pregnancy: pathophysiology and therapy.

Diabetes insipidus during pregnancy is an uncommon medical problem. We present a woman who developed transient central diabetes insipidus during two successive pregnancies. A water deprivation study with plasma arginine vasopressin concentrations confirmed the diagnosis and established the efficacy of 1-desamino-8-d-arginine-vasopressin (dDAVP). The patient was then successfully and safely treated through the second pregnancy with dDAVP.

Adult↗

Osmoregulation in pseudopregnant and prolactin-treated rats: comparison with normal gestation.

Osmoregulation was studied throughout rodent pregnancy focusing on the importance of the fetoplacental unit and prolactin in the observed alterations. Plasma osmolality (Posmol) and plasma sodium (PNa), similar in 8-day gravid and virgin Sprague-Dawley rats, decreased significantly by gestational day 10, reaching a nadir 8-10 mosmol/kg and 3-5 meq/l, respectively, below virgin levels by day 14 (both P less than 0.001). Despite this, plasma arginine vasopressin (PAVP) was measurable and similar in all pregnant and virgin groups. Osmotic thresholds for arginine vasopressin (AVP) secretion, similar in 8-day gravid and virgin rats, decreased 7.7 and 10.7 mosmol/kg in 12- and 14-day pregnant rats, respectively (both P less than 0.001). In contrast, Posmol decreased less than 2 mosmol/kg in 12- to 14-day pseudopregnant animals. When pseudopregnancy was prolonged to 18 days by prior hysterectomy, Posmol was only 2.6 mosmol/kg below that of cycling, hysterectomized controls. In other studies 14 days of hyperprolactinemia evoked by estradiol or treatment with ovine or rat prolactin had minimal effect on Posmol. We conclude that parallel decrements in Posmol and osmotic thresholds for AVP release occur during early rodent pregnancy, alterations that cannot be explained by gestational increases in circulating prolactin. In addition, the failure of pseudopregnancy. to mimic the hypotonicity of gestation suggests an important role for the fetoplacental unit in the osmoregulatory changes of rat pregnancy.

Animals↗

Monensin turns on microtubule-associated translocation of secretory granules in cultured rat atrial myocytes.

We have studied the effect of monensin on microtubule-associated translocation of atrial secretory granules in 5-7-day-old cultures of atrial myocytes from adult rats. Atrial granules and microtubules were localized by immunofluorescent microscopy of myocytes double-labeled with primary antibodies against atrial natriuretic polypeptide (ANP) and alpha-tubulin. In control myocytes, fluorescence due to atrial granules was predominantly localized to the perinuclear region containing the Golgi complex. After exposure for 30 minutes to monensin (0.5-5.0 microM), myocytes transiently contained conspicuous linear arrays of atrial granules associated with cytoplasmic microtubules. Thereafter, ANP fluorescence accumulated in subsarcolemmal foci at the cell periphery, while perinuclear ANP fluorescence faded. The monensin-induced redistribution of atrial granules was observable in both serum-containing and serum-free media and was unaffected by reducing external Ca2+ to low values, by inhibition of sarcoplasmic reticulum Ca2+ release with ryanodine, or by both. The redistribution was prevented by pretreatment with nocodazole, which fragmented microtubules and scattered Golgi complexes and the associated atrial granules throughout the cytoplasm. Radioimmunoassay showed that monensin seemingly decreased the rate of ANP secretion into the medium from 0.15 to 0.11 fmol/(hr.myocyte). These results suggest that monensin turns on microtubule-associated translocation of atrial granules from the perinuclear areas to the cell periphery by modifying the interaction between microtubules and atrial granules. Monensin also promotes movement of atrial granules along the microtubules but does not accelerate the release of ANP.

Animals↗

Water homeostasis and vasopressin release during rodent and human gestation.

Body tonicity decreases during both human and rodent gestation, manifested by a decrease in Posm of approximately 10 mosm/kg. In humans, the decrease in the osmotic threshold for thirst may precede decrements in the arginine vasopressin (AVP) secretory threshold by several weeks, whereas the metabolic clearance rate of AVP appears markedly increased in the third trimester. The cause of these osmoregulatory changes are unclear, since through 1986 we have been unable to implicate placental extracts, estrogens, progesterone, prolactin, angiotensin II, and certain endorphins in the decreased Posm observed during rat pregnancy. Changes also occur in volume-AVP secretory relationships in pregnancy. For instance, the volume-sensing AVP release mechanisms are altered during gestation in Sprague-Dawley rats in such a way that the increased intravascular volume is recognized as normal.

Animals↗

Volume homeostasis during pregnancy in the rat.

This article reviews alterations in volume and sodium handling during rat pregnancy, noting similarities and contrasts to events in human gestation. Gravid rodents undergo extracellular and plasma volume increases of 50% to 70%, and these changes accompany a marked cumulative sodium retention shared by both dam and fetuses. Pregnancy alters several factors, with opposing effects on renal salt handling; however, mechanisms by which gestational sodium accumulation and volume expansion are achieved remain obscure. Furthermore, despite substantial increases in absolute blood volume, considerable uncertainty exists as to how this volume is sensed, particularly during the final gestational week when a rapid increase in volume is associated with decreases in peripheral resistance and BP. Attempts to assess "effective" intravascular volume by measuring responses to intravenous (IV) or oral sodium loading or to chronic mineralocorticoid administration indicate that pregnant and nonpregnant rats respond similarly, suggesting that such animals sense their volume as normal. In contrast, when salt-restricted, gravid rats fail to expand their plasma volume normally; this relative hypovolemia activates mechanisms leading to free water retention and pathologic hyponatremia, responses not observed in virgin animals.

Animals↗

Plasma catecholamine responses to physiologic stimuli in normal human pregnancy.

The dynamic response of the sympathoadrenal system was evaluated during and after pregnancy in 13 healthy women with a protocol that compared cardiovascular parameters and plasma catecholamine levels during the basal state, after postural maneuvers, and following isometric exercise. Plasma epinephrine and norepinephrine levels were similar during and after gestation when the women rested on their sides, but heart rate was greater in pregnancy. Ten minutes of supine recumbency produced minimal changes, but attenuation of the anticipated increases in heart rate and plasma norepinephrine levels during standing and isometric exercise were observed during pregnancy. In contrast, alterations in plasma epinephrine appeared unaffected by gestation. Plasma renin activity and aldosterone levels were, as expected, greater during pregnancy; however, increments in response to upright posture were similar in pregnant and postpartum women. To the extent that circulating catecholamines may be considered indices of sympathoadrenal function, these data suggest that normal pregnancy alters cardiovascular and sympathetic nervous system responses to physiologic stimuli.

Adolescent↗

Effect of ovarian sex steroids on osmoregulation and vasopressin secretion in the rat.

Effects of sex steroids on osmoregulation were studied in intact and ovariectomized Sprague-Dawley rats treated for 2 wk with subcutaneously implanted hormone pellets containing 0.5 mg 17 beta-estradiol (E2) alone (group 1) or combined with 50 mg progesterone (PG; group 2) and 5.0 mg E2 alone (group 3) combined with PG (group 4). An additional group (5) of animals was given 14 daily injections with 100 micrograms/100 g body weight of E2. Controls for each group received vehicle alone. There were no alterations in basal plasma osmolality (Posmol) or vasopressin (PAVP), except for group 3 in which a small (2.5 mosmol/kg) decrement in Posmol was observed. However, mean PNa was decreased (0.9-3.4 meq/l) in hormone-treated rats, and alterations in Pglucose and/or Purea could not explain the Na-osmolal discrepancy. Intraperitoneal hypertonic saline resulted in stepwise increases in both Posmol and PAVP. Regression analysis of PAVP on Posmol demonstrated similar osmotic thresholds for AVP release in estrogen and control rats, but the slope (sensitivity of the response) was significantly (P less than 0.005) greater in hormone-treated animals. In contrast, the PAVP response to isosmotic volume depletion was not altered by estrogen. The enhanced response to osmotic stimuli could not be explained by alterations in plasma volume or pituitary AVP content and differed from PAVP -Posmol relationships observed by us previously in gravid rats. In other experiments Posmol and PAVP were similar during all stages of the estrus cycle, while Posmol was approximately equal to 10 mosmol/kg lower in 21-day gravid rats. These data demonstrate that, although estradiol has little effect on basal osmoregulation or hemodynamically mediated AVP release, PAVP responses to osmotic stimuli are markedly enhanced. These osmoregulatory effects, however, differ from those observed during rodent gestation.

Animals↗

Osmoregulation and vasopressin secretion during pregnancy in Brattleboro rats.

Osmoregulation during pregnancy was compared in Brattleboro rats completely lacking vasopressin [homozygous (DI)], those with partial deficiency [heterozygous (HZ)], and control Long-Evans (LE) animals. Plasma osmolality (Posmol) was decreased 10-16 mosmol/kg near term in each group, whereas urine osmolality (Uosmol) was similar to that of virgin controls. This was accompanied by significant increments in water turnover similar in HZ and LE and massive in the gravid DI. Chronic vasopressin treatment increased Uosmol less in pregnant DI compared with virgins (P less than 0.001), and urinary prostaglandin E2 was increased in all gravid groups. Captopril per os failed to implicate the renin-angiotensin system in the altered water ingestive behavior of pregnancy. Basal arginine vasopressin pressure (PAVP) was similar in gravid and virgin HZ and LE, whereas the osmotic threshold for AVP secretion was lower in both pregnant groups. Increasing Posmol by dehydration or hypertonic saline led to similar increments in plasma AVP (PAVP) in pregnant and nongravid rats of each group, but sensitivity of the system delta P AVP/delta P osmol was significantly lower in HZ, a difference compatible with the decreased pituitary AVP content in the HZ strain. Data are consistent with decreases in the osmotic thresholds for AVP release (in HZ and LE) and thirst (in DI) and a need for increased AVP secretion during pregnancy.

Animals↗

Medical evaluation of the pregnant patient requiring nonobstetric surgery.

This article provides a summary of currently available information from a broad range of disciplines aimed at guiding the physician caring for the pregnant patient who requires nonobstetric surgery. An understanding of the anatomic and physiologic alterations that occur during pregnancy will allow such procedures to be accomplished with morbidity and mortality approaching those of nonpregnant surgical patients. The presence of the fetus does impose some restraint; however, this should rarely impair appropriate diagnosis and treatment of maternal disease. This obtains from the broad range of diagnostic and therapeutic alternatives available, and from the fact that what is beneficial for maternal health is generally best for the fetus.

Analgesics↗

Role of volume in the regulation of vasopressin secretion during pregnancy in the rat.

We previously observed that osmoregulation and the osmotic threshold for antidiuretic hormone secretion were altered during pregnancy in Sprague-Dawley rats and the present study evaluated the influence of volume on arginine vasopressin (AVP) release during gestation in this species. Basal plasma osmolality (Posm) and intravascular volume were 297 +/- 3 mosmol/kg and 16.2 +/- 1.2 ml in virgin animals compared with 290 +/- 2 mosmol/kg and 20.2 +/- 2.3 ml in 14-d pregnant rats and 287 +/- 3 mosmol/kg and 25.2 +/- 2.3 ml in 21-d (near-term) pregnant rats (P less than 0.001, each pregnant group vs. virgin). Isosmotic volume depletion was produced by intraperitoneal polyethylene glycol. Volume decreased from 1 to 26% and blood pressure remained stable during decrements as high as 16%. Plasma AVP (PAVP) did not rise significantly in either group of pregnant animals or virgin controls until blood volume depletion reached 6-7%, after which levels rose in a similar exponential manner in virgin, 14-d, and 21-d pregnant animals. In terms of absolute changes, however, PAVP in gravid rats started to increase when intravascular volume was still considerably greater than basal blood volume in the nonpregnant controls. Other experiments, where Posm was increased by intraperitoneal hypertonic saline, reconfirmed that the osmotic threshold for AVP secretion was reduced congruent to 10 mosmol/kg during pregnancy and that AVP release was stimulated by increments in body tonicity as small as 1-2%. In parallel studies, blood volume contraction and increases in Posm were evoked by intraperitoneal polyethylene glycol dissolved in hypertonic saline and results compared with animals receiving intraperitoneal saline alone. Decrements in volume (congruent to 7%), which alone would increase PAVP minimally, increased the sensitivity of the secretory response to changes in osmolality two- to three-fold, an effect which was similar in virgin and gravid animals. Finally, restricting water intake of pregnant rats to that of virgins on days 16-20 of gestation led to suboptimal volume expansion, hypertonicity, and an exaggerated increase in PAVP. These results demonstrate that despite an intravascular space which at term is nearly twice that of virgin rats, pregnant animals secrete AVP in response to fractional volume depletion in a manner similar to nonpregnant controls; that is, the relationship between total blood volume and AVP secretion is altered during gestation such that the expanded blood volume is recognized as normal.

Animals↗