PubMed Health⌕ Search

Biomedical subjects

M G Ervin

Publications and source records attributed to M G Ervin.

At least 37 records · Page 2Linked to original sources

Postnatal renal adaptation in preterm and term lambs.

The present experiments determined if increases in renal reabsorptive capacity during the transition from fetal to neonatal life are gestation dependent. Renal function was studied in chronically-catheterized fetal lambs (133 +/- 1 days; term, 145-150 days). Additionally, renal function was studied in anaesthetized, ventilated, caesarean-delivered preterm lambs (109-139 days gestation) and term lambs (148 days gestation), and in 2-day-old spontaneously-delivered term lambs. Newborns < or = 120 days old received surfactant to facilitate ventilation and maintenance of physiologic blood gases. Two hours after caesarian delivery, urine osmolality, urine flow, glomerular filtration rate (GFR), and fractional sodium excretion (FENa) values were similar for all gestations. Relative to fetal values, caesarean-delivered newborn renal values included lower urine flow rates (0.20 +/- 0.03 v. 0.05 +/- 0.01 mL min-1 kg-1), higher urine osmolalities (118 +/- 15 v. 422 +/- 16 mOsmol kg-1 H2O), and no differences in GFR or FENa. Relative to caesarean-delivered newborns, 2-day newborn renal function included higher values for GFR (0.7 +/- 0.1 v. 3.0 +/- 0.1 mL min-1 kg-1) and urine osmolality (724 +/- 32 mosmol kg-1 H2O), and lower FENa (7.0 +/- 1.5 v. 0.2 +/- 0.02%), and urine flow (0.005 +/- 0.003 mL min-1 kg-1). The 132- and 139-day animals were ventilated for 5 h and 10 h respectively; the only functional change at 10 h was a decrease in FENa (7.0 +/- 1.5 v. 2.8 +/- 0.1%). It is concluded that: (1) relative to fetal animals, renal adaptive responses in anaesthetized, ventilated newborns begin within 2 h following caesarian delivery; (2) initial adaptive responses are not gestation dependent after 109 days; and (3) the combined effects of ventilation and/or anaesthesia delay postnatal renal adaptations for at least 10 h after birth.

Absorption↗

DDAVP-induced maternal hyposmolality increases ovine fetal urine flow.

Fetal urine flow is influenced by fetal intravascular volume, glomerular filtration rate, tubular reabsorption, and fluid regulatory hormones. As maternal-to-fetal fluid transfer is dependent on hydrostatic and osmotic gradients, we postulated that a chronic decrease in maternal plasma osmolality would promote transplacental fluid transfer and increase fetal urine flow. Six pregnant ewes and singleton fetuses (131 +/- 2 days; term = 150 days) received bladder and hindlimb arterial and venous catheters. After 5 days, plasma and urine composition, urine flow rate (Uvol), and plasma arginine vasopressin (AVP) levels were measured during a 2-h control period. At 2 h, tap water (2 liter, 38 degrees C) was administered to the ewe. At 3 h, ewes received a 20-micrograms bolus of 1-desamino-[D-Arg8]vasopressin (DDAVP), followed by continuous infusion (4 micrograms/h). In response to water loading, maternal urine osmolality decreased (761 +/- 158 to 339 +/- 13 mosmol/kgH2O), and Uvol increased. After DDAVP, maternal urine osmolality increased (1,270 +/- 89 mosmol/kgH2O), and Uvol, hematocrit, plasma osmolality (304 +/- 1 to 284 +/- 4 mosmol/kgH2O), and protein concentration decreased. Five hours after maternal DDAVP infusion, fetal plasma osmolality decreased (300 +/- 1 to 281 +/- 3 mosmol/kgH2O), and Uvol increased (0.4 +/- 0.1 to 1.3 +/- 0.2 ml/min) and remained elevated at 24 h. There was no change in fetal plasma DDAVP (immunoreactive AVP) levels or fetal urine osmolality. Controlled changes in maternal plasma osmolality may prove useful in modulating fetal urine flow and, ultimately, amniotic fluid volume.

Animals↗

Ovine fetal swallowing response to intracerebroventricular hypertonic saline.

In the near-term ovine fetus, systemic hyperosmolality stimulates dipsogenic responses. Putative systemic dipsogens (hypertonicity, angiotensin II) may initiate responses by stimulation of select cerebral circumventricular nuclei lacking a blood-brain barrier. To investigate whether central osmotic-dipsogenic mechanisms are functional in utero, fetal swallowing responses to intracerebroventricular (i.c.v.) hypertonic saline were examined. Five pregnant ewes with singleton fetuses (128 +/- 1 days gestation) were prepared with fetal lateral cerebral ventricle and vascular catheters, electrocortical (ECoG) electrodes, and electromyogram wires on the fetal thyrohyoid muscle, nuchal and thoracic esophagus, and diaphragm and studied for a minimum of 5 days postoperatively. After a 2-h basal period, fetuses received an i.c.v. infusion of artificial cerebrospinal fluid followed by successive 30-min infusions of hypertonic NaCl in artificial cerebrospinal fluid (500 and 700 mosmol/kgH2O). In response to the i.c.v. hypertonic NaCl infusions, fetal swallowing significantly increased (1.4 +/- 0.4 to 3.9 +/- 1.4 and 2.9 +/- 0.5 swallows/min low-voltage ECoG, respectively). Plasma arginine vasopressin levels increased, although the change was not statistically significant (9.1 to 24.2 pg/ml; P = 0.07), and there was no change in fetal plasma osmolality, sodium concentration, or ECoG activity. Together with previous studies, these results indicate that both central and systemic osmotic dipsogenic mechanisms are functional in utero.

Animals↗

Postnatal cardiovascular and metabolic responses to a single intramuscular dose of betamethasone in fetal sheep born prematurely by cesarean section.

Although the benefits of antenatal hormone treatment are well accepted, most studies have reported only pulmonary effects. There is evidence of beneficial cardiovascular and metabolic effects in studies using chronically catheterized animals; however because of the route of administration, the results are not directly applicable to clinical strategies. We previously demonstrated significant pulmonary effects in animals treated antenatally with a single, direct fetal, intramuscular injection of glucocorticoids. This study was performed to determine the effects of a single fetal injection of betamethasone (BETA) alone or in combination with thyroxine (T4) on cardiovascular and metabolic responses after preterm birth. Hemodynamic and metabolic responses at birth were determined in fetuses (126-d gestation; term = 150 d) treated with ultrasound-guided intramuscular injections of 0.5 mg/kg BETA (n = 7), BETA plus 60 g/kg T4 (n = 7), or saline (SAL, n = 9). After 48 h, lambs were delivered by cesarean section and studied for 3 h. BETA treatment increased mean arterial blood pressure [56 +/- 6 (SEM) versus 42 +/- 3 mm Hg], heart rate (152 +/- 5 versus 123 +/- 4 beats/min), and cardiac output (467 +/- 17 versus 349 +/- 36 mL/min/kg) versus SAL. Responses of BETA+T4-treated animals were not different from animals treated with BETA alone. Glucose and FFA were similar among all groups. The increase in catecholamine levels normally seen at birth was significantly attenuated in both the BETA and BETA+T4-treated animals. A single, intramuscular injection of glucocorticoids 48 h before delivery improves cardiovascular responses to preterm birth. This effect is not augmented by concomitant administration of T4.

Animals↗

Ontogeny of ovine fetal renal atrial natriuretic factor receptors.

Ovine fetal renal responses to ANF decrease during the last third of gestation, although circulating fetal plasma atrial natriuretic factor (ANF) levels are higher than in the maternal circulation, and do not change with gestation. This study examined whether previously reported maturational changes in fetal renal responses to ANF are due to changes in renal ANF receptor numbers and/or affinity during gestation. ANF receptor numbers (Bmax) and dissociation constants (Kd) were measured in isolated renal glomeruli from early (95 and 110 day; mean 103 +/- 2) and late gestation (131 and 145 day; mean 138 +/- 2) fetal and maternal sheep. Fetal renal ANF receptor Bmax values significantly increased between 103 and 138 days gestation (13 +/- 3 to 29 +/- 4 fmol/mg protein) but were significantly lower than maternal values (60 +/- 13 fmol/mg protein). Fetal ANF receptor Kd values also increased significantly (245 +/- 34 to 370 +/- 36 pM), with early gestation values significantly lower than maternal values (470 +/- 69 pM). Thus, the blunted fetal renal response to ANF in late as compared to early gestation is not due to reduced ANF receptor numbers. Rather, an increased proportion of ANF clearance receptors, reduced post-receptor function and/or altered intrarenal hemodynamics may contribute.

Animals↗

Adenosine mediates hypoxic release of arginine vasopressin in fetal sheep.

The effects of adenosine on plasma arginine vasopressin (AVP) concentrations were determined in chronically catheterized fetal sheep (> 0.8 term). Infusion of adenosine [0.35 +/- 0.01 (SE) mg.min-1.kg-1] into the inferior vena cava of six fetuses caused a transient fall in arterial PO2 (by approximately 3 Torr), a slight reduction in arterial pH, and a 5- to 6-mmHg decrease in diastolic pressure without significantly affecting systolic or mean arterial values. A lower rate of infusion (0.19 +/- 0.01 mg.min-1 x kg-1) in five fetuses had virtually no effect on arterial blood gases, pH, or arterial pressures. Both the low- and high-dose adenosine infusions significantly increased fetal plasma AVP concentrations (1.7 +/- 0.2 to 25 +/- 7 pg/ml and 1.6 +/- 0.1 to 54 +/- 8 pg/ml, respectively). Intravenous infusion of papaverine lowered fetal diastolic and mean arterial pressures by approximately 8 mmHg but had no significant effect on plasma levels of AVP. During an hour of isocapnic hypoxia (arterial PO2 12-13 Torr), fetal plasma AVP levels increased from 1.7 +/- 0.2 to 40 +/- 6 pg/ml. Intra-arterial infusion of the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline significantly blunted the hypoxia-induced rise in plasma AVP concentrations to a maximum mean level of 11 +/- 6 pg/ml. These results indicate that 1) adenosine causes a dose-dependent increase in plasma AVP concentrations and 2) a hypoxia-induced rise in fetal adenosine levels triggers vasopressin release.

Adenosine↗

Vascular effects alter early-gestation fetal renal responses to vasopressin.

Distinct receptors mediate the vascular (V1) and renal (V2) effects of arginine vasopressin (AVP). Although ovine fetal AVP-induced antidiuresis can be demonstrated in early gestation (< 120 days; term 150 days), the early-gestation fetal renal responses to AVP are variable, including increases in urine flow and glomerular filtration rate (GFR). AVP V1 receptor predominance and/or V2 receptor system immaturity may contribute to variable early-gestation renal responses to AVP. To differentiate these possibilities, we assessed early-gestation fetal V2 receptor function in the presence and absence of V1 receptor-mediated effects by comparing the responses to AVP (a combined V1-V2 receptor agonist; n = 10; 112 +/- 2 days) with the selective V2-receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) (n = 5; 111 +/- 2 days). AVP infusion increased fetal mean arterial pressure (MAP; 36 +/- 1 to 44 +/- 2 mmHg) and decreased heart rate (197 +/- 2 to 171 +/- 3 beats/min); DDAVP infusion had no effect on MAP or heart rate. Free water clearance decreased in response to AVP (0.13 +/- 0.02 to 0.02 +/- 0.01 ml.min-1.kg-1) and DDAVP (0.21 +/- 0.04 to 0.04 +/- 0.02 ml.min-1.kg-1), and urine osmolality increased in response to both analogues (AVP: 145 +/- 4 to 283 +/- 15 mosmol/kgH2O; DDAVP: 146 +/- 5 to 244 +/- 32 mosmol/kgH2O).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ovine fetal swallowing and renal responses to oligohydramnios.

Amniotic fluid (AF) volume regulation is dependent on a balance between fluid production and fluid resorption. We examined the effects of reduced AF volume on AF production by fetal urine and resorption by fetal swallowing and the response of these parameters to AF volume replacement. Eight time-dated pregnant ewes (125 +/- 1 days gestation) were studied before (day 1) and after (day 3) AF and fetal urine drainage. Drainage resulted in a significant decrease in AF volume (415 +/- 89 to 157 +/- 36 ml). Fetal urine osmolality increased (139 +/- 10 to 286 +/- 33 mosmol/kgH2O), while urine flow did not change significantly (0.31 +/- 0.04 to 0.23 +/- 0.06 ml/min), resulting in nonsignificant increases in osmolar, sodium, and chloride excretions. Fetal electromyographic swallowing activity decreased 30% (1.0 +/- 0.1 to 0.7 +/- 0.1 swallows/min; P < 0.05), while net esophageal flow decreased 74% (0.31 +/- 0.12 to 0.07 +/- 0.04 ml/min; P < 0.05). On day 4, 0.15 M NaCl (500 ml; 37 degrees C) was administered into the AF over 30 min. During the 2 h after reinfusion, urine flow (0.29 +/- 0.07 to 0.40 +/- 0.09 ml/min) and osmolar sodium and chloride excretion significantly increased, though fetal swallowing activity and esophageal flow did not change. Thus the ovine fetus responded to reduced AF volume by maintaining AF production and decreasing AF resorption. In response to AF replacement, urine flow increased while fetal swallowing activity did not change, consistent with an intramembranous pathway for fetal AF resorption.

Amniotic Fluid↗

Central angiotensin II stimulation of ovine fetal swallowing.

In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation.

Amniotic Fluid↗

Multiple receptor contributions to ovine fetal cardiovascular responses to vasopressin.

Selective AVP V1 receptor antagonist and V2 receptor agonist treatments were used to study V1 and V2 receptor contributions to AVP-induced effects on ovine fetal blood pressure, heart rate, and renal function. The results indicate that V1 receptors do not contribute to late gestation fetal renal responses to AVP. The pressor response to AVP was abolished by V1 receptor blockade while the heart rate response was not affected (Fig. 1). This separation of the blood pressure and heart rate responses to AVP has been noted previously, and indicates that AVP-induced fetal bradycardia is not a reflex response to increased blood pressure. A direct V1 receptor-mediated effect on the heart also appears unlikely. The absence of a dDAVP effect on fetal heart rate indicates that AVP-induced bradycardia is not a V2 receptor-mediated event. An AVP effect on oxytocin receptors appears unlikely due to the antioxytocic action of the Manning Compound. Demonstration of AVP V1a receptors in and around the brainstem cardiovascular control centers supports the view that circulating AVP can modulate vagal outflow via effects in the area postrema. However, if Manning Compound infusion blocks fetal V1a receptor-mediated vascular responses and V1b receptor-mediated ACTH release, then blockade of the heart rate response to AVP also would have been expected. In summary, the fetal heart rate response to AVP is not dependent on AVP-induced increases in blood pressure, V1 receptors blocked by the Manning Compound, or V2 receptors stimulated by dDAVP. We conclude that AVP contributes to fetal heart rate regulation, and the effect is not mediated by any known population of AVP receptors.

Animals↗

Fetal endocrine and renal responses to in utero ventilation and umbilical cord occlusion.

OBJECTIVE: Fetal to neonatal transition involves a myriad of endocrine and renal adaptive changes triggered by multiple simultaneous stimuli. We examined the extent to which ventilation and umbilical cord occlusion have an impact on the many endocrine and renal function changes in fetal sheep at 133 +/- 1 day of gestation. STUDY DESIGN: Nine fetuses were chronically prepared with an endotracheal tube, vascular and bladder catheters, and an inflatable umbilical cord occluder. After a 2-hour control period fetuses were treated with commercially prepared surfactant and ventilated with 100% oxygen. One hour after the onset of stable ventilation the umbilical cord was occluded and the animals were monitored for 3-hours. RESULTS: In response to ventilation fetal arterial PO2 increased (18 +/- 1 to 86 +/- 29 mm Hg) and remained significantly above control values after cord occlusion. Fetal arterial pH, hematocrit, and mean arterial pressure and heart rate did not change during the study. Ventilation alone evoked significant increases in epinephrine and norepinephrine concentrations. Renal responses to ventilation included significant decreases in urine flow rate, fractional sodium excretion, and fractional water excretion. Neither ventilation nor cord occlusion resulted in significant changes in plasma concentrations of atrial natriuretic factor, arginine vasopressin, and angiotensin II or in glomerular filtration rate, urine osmolality, free water, and osmolar clearances. CONCLUSIONS: (1) Mechanical ventilation and oxygenation alone increase circulating fetal catecholamine levels. (2) The addition of umbilical cord ligation has minimal impact on fetal endocrine and renal adaptive responses.

Animals↗

Maternal/fetal dehydration: prolonged effects and responses to oral rehydration.

Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration.

Animals↗

Ovine fetal swallowing and behavioral state responses to sublingual water.

Ovine fetal swallowing primarily occurs in bouts of activity associated with low voltage electrocorticogram activity and breathing movements. Despite similar rates of electromyographic swallowing activity, there are significant differences in the net esophageal fluid flow among fetuses. To determine if variations in the volume of fluids accessible to the fetus (amniotic fluid, lung fluid, salivary secretions) affect fetal swallowing, we studied the effects of sublingual distilled water infusions on ovine fetal swallowing rates and esophageal flow. Seven pregnant ewes at 127 +/- 2 days gestation were chronically instrumented with maternal and fetal vascular catheters, fetal electrocortical, electro-ocular and electromyograph electrodes, an esophageal flow probe and a sublingual infusion catheter. Following a 2-hour control period, consecutive sublingual infusions of room temperature distilled water (10 and 20 ml/kg/h) were administered for 2 h each. In response to sublingual infusions, fetal plasma sodium (142.5 +/- 0.5 to 140.8 +/- 0.8 mEq/l), chloride concentrations (109.2 +/- 0.4 to 107.7 +/- 0.7 mEq/l) and osmolality (302 +/- 2 to 298 +/- 2 mOsm/kg) decreased significantly. Swallowing activity and esophageal flow did not change significantly from basal values (47 +/- 9 swallows/h, 19.2 +/- 4.2 ml/h) during the sublingual infusions. However, fetal low-voltage electrocortical activity increased significantly during both infusion periods (42 +/- 3 to 56 +/- 6%). Sublingual distilled water infusion decreases fetal plasma osmolality and alters fetal behavioral state without affecting swallowing frequency or esophageal flow.

Administration, Sublingual↗

Fetal catecholamine, cardiovascular, and neurobehavioral responses to cocaine.

OBJECTIVE: Although maternal cocaine administration results in fetal cardiovascular and behavioral alterations, these responses have been attributed to hypoxia resulting from reduced uteroplacental blood flow. We studied the fetal catecholamine, cardiovascular, and neurobehavioral responses to direct fetal cocaine administration. STUDY DESIGN: Cardiovascular, electrocortical, and electroocular responses and plasma catecholamines were monitored in chronically catheterized fetal sheep (n = 7), 127 +/- 2 days' gestation, during a control period and after intravenous fetal injections of cocaine 0.5 and 1.0 mg/kg. RESULTS: Intravenous cocaine caused prompt increases in fetal plasma norepinephrine (372 +/- 73 to 531 +/- 112 and 842 +/- 233 pg/ml), epinephrine (27 +/- 7 to 46 +/- 13 and 49 +/- 11 pg/ml), and systolic blood pressure (46 +/- 2 to 53 +/- 2 and 55 +/- 2 mm Hg). Low-voltage electrocortical activity decreased from 61.7% +/- 3.0% to 38.4% +/- 3.9% in the first hour after the cocaine 0.5 mg/kg dose but recovered to baseline values during the second hour. After the cocaine 1.0 mg/kg dose, low-voltage electrocortical activity decreased to 40.7% +/- 2.0% and did not recover thereafter. Fetal blood gas values did not change. CONCLUSION: Direct fetal cocaine administration increases fetal plasma catecholamine levels and fetal blood pressure and suppresses low-voltage electrocortical activity. Chronic cocaine exposure may hamper central nervous system maturation and alter postnatal development.

Animals↗

Myometrial contractile responsiveness to oxytocin after dexamethasone suppression of circadian uterine activity in pregnant rhesus macaques during late gestation.

OBJECTIVE: This study was designed to determine if dexamethasone alters myometrial responsiveness to oxytocin or oxytocin secretion. STUDY DESIGN: Studies were conducted in rhesus macaques (n = 6), between 144 and 148 days' gestation (term 167 days). The first study was conducted at 9 AM and repeated 36 hours later at 9 PM. At 9 AM the following morning a continuous maternal dexamethasone infusion (15 micrograms/kg/hr given intravenously) was initiated, and the study was repeated at 9 PM, 60 hours later. Four doses of oxytocin (500, 1000, 2000, and 4000 pg/kg/min) were administered as 1-minute pulses every 5 minutes for 30 minutes. The number of contractions per pulse (contraction/pulse ratio) was used to determine differences in myometrial responsiveness. RESULTS: Before dexamethasone infusion there was a circadian rhythm in uterine activity with peak contractile events between 8 and 10 PM (p < 0.01), whereas during infusion the rhythm was ablated. At oxytocin dose 1, the 9 AM contraction/pulse ratio (0.3 +/- 0.1) was lower than that for 9 PM (0.6 +/- 0.2) and for 60 hours later (0.6 +/- 0.1) (mean +/- SE, p < 0.05). Similar results were observed at dose 2, whereas no differences in the contraction/pulse ratio were noted at dose 3. Basal plasma oxytocin concentrations were unaffected by dexamethasone treatment, whereas plasma estradiol and cortisol concentrations were reduced compared with control values (p < 0.01). CONCLUSIONS: (1) There is a differential sensitivity to oxytocin between morning and evening and (2) the dexamethasone-induced loss of the uterine contractile rhythm is not the result of a loss of myometrial sensitivity to oxytocin or to a suppression of plasma oxytocin concentrations.

Animals↗

Dehydration increases the renal response to atrial natriuretic peptide in fetal sheep.

OBJECTIVE: In sheep, maternal water deprivation results in urinary natriuresis in spite of suppression of plasma atrial natriuretic factor levels. Near-term fetal sheep also have a urinary natriuresis without change in plasma atrial natriuretic factor during maternal dehydration. This study was designed to explore the role of plasma atrial natriuretic factor levels in fetal dehydration-natriuresis. STUDY DESIGN: Eight chronically instrumented preterm (113 +/- 1 days) ovine fetuses received two atrial natriuretic factor infusions (3 and 15 ng/kg/min) in a euhydrated state and after 48 +/- 1 hours of maternal water deprivation. RESULTS: Dehydration significantly increased maternal plasma osmolality (302 +/- 2 to 313 +/- 2 mOsm/kg water), sodium (148.1 +/- 0.8 to 154.3 +/- 0.4 mEq/L), chloride (112.4 +/- 0.6 to 116.8 +/- 0.9 mEq/L), and arginine vasopressin (4.2 +/- 1.2 to 23.0 +/- 4.0 pg/ml) and significantly decreased plasma atrial natriuretic factor (36 +/- 6 to 19 +/- 4 pg/ml) concentrations. Fetal plasma osmolality (296 +/- 1 to 308 +/- 2 mOsm/kg), atrial natriuretic factor (128 +/- 16 to 241 +/- 36 pg/ml), and arginine vasopressin (3.5 +/- 0.8 to 12.3 +/- 4.8 pg/ml) concentrations and urine osmolality (170 +/- 10 to 253 +/- 10 mOsm/kg), osmolar clearance (0.80 +/- 0.02 to 0.14 +/- 0.02 ml/kg/min), and fractional sodium excretion (3.3% +/- 1.7% to 8.5% +/- 2.1%) increased significantly with dehydration, whereas the plasma atrial natriuretic factor clearance decreased from 127 +/- 27 to 63 +/- 10 ml/kg/min. Dehydration had no effect on fetal hematocrit, vascular pressures, glomerular filtration rate, urine flow, or free water clearance. In euhydrated fetuses plasma atrial natriuretic factor increased from 128 +/- 16 to 287 +/- 46 pg/ml with sequential atrial natriuretic factor infusion, and no significant increases were observed in urine flow, fractional sodium excretion, and glomerular filtration rate. In contrast, atrial natriuretic factor infusion to dehydrated fetuses significantly increased urine flow (0.17 +/- 0.03 to 0.32 +/- 0.07 ml/kg/min), osmolar clearance (0.14 +/- 0.02 to 0.28 +/- 0.06 ml/kg/min), and fractional sodium excretion (8.5% +/- 2.1% to 14.8% +/- 4.0%). CONCLUSION: These results demonstrate that in the fetus at 113 days' gestation plasma atrial natriuretic factor levels increase with dehydration, probably a result of decreased plasma atrial natriuretic factor clearance, and the fetal renal responsiveness to atrial natriuretic factor infusion increases during maternal dehydration.

Animals↗

Ovine maternal and fetal renal vasopressin receptor response to maternal dehydration.

OBJECTIVE: Arginine vasopressin secretion increases in response to increased plasma osmolality or hypovolemia. Dehydration-induced increases in plasma arginine vasopressin levels have been shown to down-regulate arginine vasopressin V2 receptors in adult rat kidneys. Our study determined ovine maternal and fetal renal arginine vasopressin receptor characteristics and receptor response to maternal dehydration. STUDY DESIGN: Eight pregnant ewes (113 +/- 1 days) were dehydrated for 72 hours; eight animals served as controls. Renal medullary tissue was isolated from maternal and fetal kidneys, and arginine vasopressin receptor characteristics determined with saturation and competition assays using tritiated arginine vasopressin, arginine vasopressin, and arginine vasopressin analogs. RESULTS: Euhydrated maternal and fetal renal medullary arginine vasopressin receptor dissociation constant (3.0 +/- 0.3 and 1.9 +/- 0.3 nmol/L) and maximal binding capacity (149 +/- 15 and 111 +/- 33 fmol/mg protein) values were similar. Pharmacologic profiles with selective agonists indicated a predominance of V2 receptors. Dehydration significantly increased maternal and fetal plasma osmolalities (304 +/- 2 to 320 +/- 2; 296 +/- 1 to 319 +/- 3 mOsm/kg water, respectively) and arginine vasopressin levels (3.8 +/- 1.4 to 29.3 +/- 4.6; 4.4 +/- 1.0 to 16.9 +/- 5.0 pg/ml, respectively) but had no effect on arginine vasopressin receptor binding. CONCLUSION: Specific, saturable, single-site tritiated arginine vasopressin binding is present in ovine maternal and fetal renal medullary membranes. Ovine maternal and fetal renal arginine vasopressin receptors do not down-regulate in response to dehydration-induced elevations in plasma arginine vasopressin levels.

Animals↗