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Biomedical subjects

C R Rosenfeld

Publications and source records attributed to C R Rosenfeld.

At least 19 recordsLinked to original sources
PubMed1996

Angiotensin II receptor characteristics and subtype expression in uterine arteries and myometrium during pregnancy.

The uteroplacental vasculature is less sensitive to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature. Although the mechanism(s) responsible is unclear, uterine arteries (Ua) may demonstrate ANG II receptor (AT receptors) down-regulation or expression of AT2 receptors, which do not mediate vasoconstriction. We determined AT receptor binding characteristics and subtype expression in Ua from normotensive pregnant (n = 14; 38 +/- 0.5 weeks gestation) and nonpregnant (n = 28) women. Comparative studies were performed with myometrium, a nonvascular smooth muscle. We measured binding density (Bmax) and affinity (Kd) in plasma membrane preparations employing radioligand binding. Receptor subtypes were assessed by inhibiting [125I]ANG II binding with specific antagonists. During pregnancy, the Ua Bmax and Kd were unchanged (P > 0.1; 221 +/- 36 vs. 159 +/- 27 fmol/mg protein and 0.8 +/- 0.1 vs. 0.9 +/- 0.1 nmol/L, respectively). However, myometrial Bmax decreased 92% (580 +/- 129 vs. 44 +/- 7 fmol/mg protein; P < 0.001), and Kd rose 4-fold (1.5 +/- 0.4 to 6.0 +/- 0.6 nmol/L; P < 0.001). AT1/AT2 expression averaged 15%/85% in Ua from nonpregnant and pregnant women, whereas in myometrium, values were 10%/90% and 60%/40%, respectively. In myometrium from laboring women (n = 8), force (1.38 +/- 0.14 to 1.59 +/- 0.12 x 10(4) N/m2; P < 0.04) and contractile frequency (0.038 +/- 0.05 to 0.116 +/- 0.014 contractions/min; P < 0.001) increased with 10(-5) mol/L ANG II and were abolished by AT1 receptor inhibition. Myometrium from nonpregnant women (n = 3) was unresponsive, and AT2 inhibition did not alter responses. In nonpregnant women, AT2 receptors predominate in Ua and myometrium. Although Ua AT receptors are unaltered during pregnancy, myometrial Bmax decreases, reflecting decreases in the expression of AT2 >> AT1 receptors and differential receptor regulation.

Angiotensin II↗
PubMed1995

Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity.

Fetal sheep appear less responsive to infused angiotensin II (ANG II) than pregnant ewes. This may reflect a greater fetal metabolic clearance rate (MCRANGII) and thus lower plasma ANG II levels. We therefore determined fetal MCRANGII, half-life (T1/2), and placental removal of ANG II. Fetal sheep (n = 13; 113-139 days of gestation) received 0.573-5.73 micrograms ANG II/min iv for 30 min while arterial pressure and heart rate were monitored. Serial blood samples were obtained before and during a 30-min infusion to measure ANG II and calculate MCRANGII and after stopping the infusion to determine T1/2. MCRANGII was similar across gestation and at doses < or = 2.29 micrograms/min (683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1 for adults) but was 30-40% lower with 5.73 micrograms ANG II/min (494 +/- 57 ml.min-1.kg-1, P < 0.05). T1/2 was 15-21 s. Fetal placental ANG II removal averaged 87 +/- 3 vs. 20 +/- 6% for uteroplacental removal; this was unaffected by dose and was linear with plasma ANG II levels, and saturation was not evident. Plasma ANG II levels rose proportionally with infusion rate and did not change significantly over time; thus fetal plasma ANG II concentrations can be predicted from MCRANGII. Measured and predicted ANG II levels at each infusion rate and time point were similar: r = 0.87, slope = 0.87 (P < 0.001). At equivalent predicted plasma ANG II levels fetal and maternal pressor responses were similar (P > 0.1); however, increases in umbilical vascular resistance exceeded those in uteroplacental vascular resistance (P < 0.03). Fetal MCRANGII is approximately 10-fold greater than maternal, partially reflecting the extensive capacity of ANG II removal by the placental circulation. Contrary to previous conclusions, fetal-maternal pressor sensitivity to ANG II does not differ, whereas the placental vasculature is more sensitive to ANG II than the uteroplacental circulation.

Angiotensin II↗
PubMed1995

Smooth muscle myosin heavy chain isoforms are developmentally regulated in male fetal and neonatal sheep.

Adult vascular smooth muscle expresses 204-kD (SM1) and 200-kD (SM2) myosin heavy chain (MHC) isoforms. Fetal vascular smooth muscle expresses another 200-kD isoform, MHC-B, that appears to be developmentally regulated. The ontogeny of expression of these MHC isoforms in vascular and nonvascular smooth muscles is not fully understood and may differ. In the present report we examined the ontogeny of these isoforms in aortic and bladder smooth muscle from male fetal (n = 12, 119-140-d gestation; term 145 +/- 5 d) and neonatal (n = 12, 1-33 d) sheep. Tissues were analyzed for total and soluble protein contents. Actin, MHC, and MHC isoforms were analyzed by SDS-PAGE using 3-20% and 4% polyacrylamide gels, respectively. The expression of the adult and fetal 200-kD MHC isoforms were determined by Western analysis. Between 119 d gestation and 33 d neonatal, age-dependent increases (p < 0.02) occurred in bladder actin (16 +/- 0.8 versus 22 +/- 1.4 micrograms/mg of wet weight), MHC (6.5 +/- 0.2 versus 9.7 +/- 1.1) and both soluble (71 +/- 2.9 versus 92 +/- 6.3) and total protein (78 +/- 3.9 versus 103 +/- 5.5). Aortic smooth muscle actin (8.5 +/- 0.7 versus 17 +/- 1.1), MHC (3.1 +/- 0.4 versus 5.2 +/- 0.5), and soluble (44 +/- 2.3 versus 61 +/- 3.0) and total protein (87 +/- 5.8 versus 108 +/- 3.2) also increased (p < 0.01). Aortic SM1 increased (r = 0.79, p < 0.001) during this time, whereas expression of the 200-kD MHC fell (r = -0.79, p < 0.001). In contrast, bladder SM1 fell (r = -0.88, p < 0.001) as the 200-kD MHC rose (r = 0.88, p < 0.001). The type of 200-kD MHC isoform expressed also differed between tissue types; bladder expressed SM2 and little or no MHC-B throughout this phase of development, whereas fetal aorta appeared to express primarily MHC-B, which decreased as adult SM2 expression rose after birth. Expression of smooth muscle proteins and MHC isoforms are developmentally regulated and tissue-dependent, the latter perhaps reflecting developmental differences in organ growth and/or function.

Actins↗
PubMed1995

The small for gestational age infant: accelerated or delayed pulmonary maturation? Increased or decreased survival?

OBJECTIVE: Small for gestational age (SGA) neonates have been considered to have accelerated pulmonary maturation and thus a lower risk for respiratory distress syndrome (RDS) than appropriate for gestational age (AGA) neonates. This, however, has not been thoroughly examined. Therefore, we compared SGA infants with AGA infants of the same gestational age (GA) with respect to risk of RDS, respiratory failure, or death. POPULATION: An indigent population born in a large county hospital. METHODS: Multivariate analyses were performed controlling for GA alone or for GA, race, sex, and congenital anomalies. Because the proper method to identify SGA infants is unclear, we performed separate analyses using different GA estimates (obstetric or pediatric) and intrauterine growth grids (hospital-specific grids or grids for a healthy, geographically-defined population). RESULTS: SGA infants did not fare better than AGA infants in any analysis. SGA infants had significantly increased risk in some analyses of RDS and in almost all analyses of respiratory failure or death. The risk associated with being SGA was generally comparable to that associated with male sex or White race. CONCLUSION: The concept that intrauterine growth retardation accelerates lung maturation and improves outcome is not supported in comparisons of SGA and AGA infants of the same GA, sex, and race. This widely accepted concept deserves critical re-evaluation.

Fetal Growth Retardation↗
PubMed1994

Angiotensin II metabolic clearance rate and pressor responses in nonpregnant and pregnant women.

OBJECTIVES: Normal pregnancy is associated with reduced pressor dose-responses to infused angiotensin II. We tested the hypotheses that alterations in the metabolic clearance rate and the half-life of angiotensin II account for reduced pressor dose-responses during gestation and that angiotensin II increases circulating levels of vasodilatory prostaglandins I2 and E2 relative to thromboxane A2. STUDY DESIGN: Eleven nonpregnant and 37 pregnant (30 +/- 0.3 weeks' gestation, mean +/- SE) women were infused with angiotensin II (3.11 to 22.36 ng/min.kg) for 15 minutes, and blood was obtained to evaluate steady-state immunoreactive plasma angiotensin II and eicosanoid concentrations. RESULTS: Angiotensin II pressor responses were dose dependent in all groups and reduced in pregnant women (p < 0.001). Basal immunoreactive plasma angiotensin II concentrations were 2.7-fold greater (p < 0.001) in pregnant versus nonpregnant women. Plasma levels reached steady state by 5 minutes of infusion, and at similar angiotensin II concentrations the increase in blood pressure was greater in nonpregnant versus pregnant women (p < 0.001). The angiotensin II metabolic clearance rate and half-life were similar in nonpregnant and pregnant women: metabolic clearance rate = 85 +/- 10 versus 68 +/- 3 ml/min.kg, respectively (p = 0.130), and half-life = 48 and 49 seconds, respectively. Plasma prostaglandin I2 (6-keto-prostaglandin F1 alpha) prostaglandin E2, and thromboxane B2 levels in pregnant women were unaffected by angiotensin II infusions. CONCLUSION: Neither changes in angiotensin II metabolism nor angiotensin II-induced increases in plasma levels of prostaglandin I2, prostaglandin E2, or the prostaglandin I2/thromboxane A2 ratio appear responsible for the decreased pressor response sensitivity to infused angiotensin II observed during normal human pregnancy.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Surfactant protein A and saturated phosphatidylcholine in respiratory distress syndrome.

We measured surfactant protein A (SP-A) by ELISA using a rabbit antihuman SP-A polyclonal antibody and saturated phosphatidylcholine (SPC) by thin-layer chromatography in sequential tracheal fluid samples obtained from 16 preterm neonates without lung disease and 37 with respiratory distress syndrome (RDS). SP-A and SPC were lower in neonates with RDS than in control infants (1.0 +/- 0.1 versus 8.9 +/- 2.2 ng SP-A/microgram protein [p < 0.0001] and 0.20 +/- 0.05 versus 0.70 +/- 0.19 mumol SPC/mg protein [p < 0.01], respectively). Initial SP-A concentrations correlated inversely with severity of RDS (r = 0.45, p < 0.01) but did not correlate with initial SPC levels. Significant increases in SP-A were detectable within 12 to 24 h after birth in neonates with RDS. Further increases occurred subsequently and were similar for neonates treated with either a synthetic (Exosurf) or a modified natural (Survanta) surfactant. Using two-dimensional gel electrophoresis, SP-A in tracheal fluid obtained during the early and recovery phases of RDS exhibited lesser degrees of posttranslational modification than SP-A forms from control neonates. Administration of Exosurf or Survanta resulted in comparable increases in SPC in tracheal fluid. Preterm neonates with RDS seem to have an immature SP-A metabolism that persists for several days after birth. The type of surfactant used does not modify the recovery of SP-A or SPC in tracheal fluid from infants with RDS.

Analysis of Variance↗
PubMed1994

Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates.

OBJECTIVE: Healthy very-low-birth-weight neonates (VLBW, < or = 1500 g) exhibit a high incidence of neutropenia according to Manroe's reference ranges for neutrophil indices. Since these reference ranges may be inappropriate for VLBW neonates, we determined the reference ranges for circulating peripheral neutrophils in VLBW neonates between birth and 28 days of age. METHODS: Serial, timed peripheral white blood cell counts (n = 1788) were prospectively obtained between birth and 28 days from 193 inborn, VLBW neonates delivered between January 1 and December 31, 1990. Data were divided into neutrophil counts obtained prior to (n = 630) and after (n = 1158) 60 hours of age. After excluding counts from neonates with perinatal and/or neonatal complications, values from "normal" neonates were compared to Manroe's reference ranges. Where indicated new ranges were developed. RESULTS: Although immature neutrophil (ATI) and immature:total neutrophil (I:T) values were within Manroe's reference ranges (P > .1) throughout the neonatal period, 67% of total neutrophil values (ATN) obtained prior to 60 hours of age were outside (P < .001) and 95% were considered neutropenic. Newly developed ATN reference ranges for VLBW neonates have a wider range of distribution compared to Manroe's results, primarily reflecting a decrease in the lower boundary. ATN values between 61 hours and 28 days also differed (P < .001), and new ranges had upper and lower boundaries of 6000 and 1100/mm3, respectively. Maternal hypertension was associated with neonatal neutropenia (P < .001) without abnormalities of ATI or I:T prior to day 3 of life; however, neutrophilia predominated after day 7. Between birth and 28 days > 70% of ATN values were abnormal in neonates with apnea, neutrophilia occurring in > 90% of counts; I:T values, however, were normal between 61 hours and 28 days. CONCLUSIONS: Normal preterm VLBW neonates have ATN reference ranges that differ significantly from that for larger, older neonates, demonstrating the effects of development on neutrophil dynamics. The predictability of neonatal infection using these new reference ranges requires additional study.

Humans↗
PubMed1993

Prediction of the severity of meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome is associated with increased neonatal morbidity and mortality. We sought to determine whether the need for neonatal mechanical ventilation or prolonged ventilation (> or = 3 days) was predictable from antepartum, intrapartum, and immediate neonatal events. STUDY DESIGN: Between 1987 and 1989, 8003 of 43,906 (18%) live infants had meconium-stained amniotic fluid; 82 of these infants had clinical and radiographic evidence of meconium aspiration, and of these 82, 39 (48%) required mechanical ventilation. Predictors of ventilation or prolonged ventilation were determined by means of stepwise logistic regression. RESULTS: Predictors of neonatal ventilation included fetal tachycardia, interval from meconium detection to delivery, low 5-minute Apgar score, respiratory distress necessitating intubation in the delivery suite, and delivery by cesarean section. Sensitivity was 72%, and specificity was 64%; the model was incorrect in 32% of the cases. Predictors of prolonged ventilation were ominous fetal heart rate tracing, umbilical arterial pH < 7.20, birth weight > 90th percentile, nulliparity, and Apgar score > 4 at 1 minute and < or = 6 at 5 minutes. Sensitivity was 67%, and specificity was 91%; prolonged ventilation was incorrectly predicted in 17% of the cases. CONCLUSIONS: Use of these models to determine the need for mechanical ventilation or prolonged ventilatory assistance will enhance identification of infants at risk of severe meconium aspiration and will lead to early transfer to the neonatal intensive care unit for intense observation and management.

Apgar Score↗
PubMed1993

Distribution of unsaturated fatty acids in phospholipids of arteries from nonpregnant, pregnant and fetal sheep.

Normal ovine pregnancy is associated with elevated levels of circulating vasodilator prostaglandins (PGs) and increases in PG production by uterine and systemic arteries. We hypothesized that the availability of fatty acid substrate may regulate PG production in vasculature from nonpregnant, pregnant and fetal sheep. In pregnant sheep, levels of arachidonic acid (20:4 omega 6), the immediate PG precursor, were significantly lower in phospholipids from uterine versus systemic (renal) arteries. Although linoleic acid (18:2 omega 6), the primary arachidonic acid precursor, was elevated (p < 0.001) in uterine arteries during pregnancy, levels in systemic arteries were decreased. Levels of omega 3 polyunsaturated fatty acids (PUFAs) also were increased (p < 0.001) in both uterine and systemic arteries during pregnancy. In fetal-placental arteries, the levels of arachidonic and linoleic acid were 50 and 90% less, respectively, than that in maternal arteries. We conclude that during ovine pregnancy vascular prostanoid production may be regulated, in part, by the availability of fatty acid precursors.

Animals↗
PubMed1993

Ontogeny of angiotensin II vascular smooth muscle receptors in ovine fetal aorta and placental and uterine arteries.

OBJECTIVE: Our purpose was to determine if differences in angiotensin II vascular smooth muscle receptor binding account for the attenuated fetal placental and systemic responses to infused angiotensin II relative to maternal responses and for the differences between umbilical and fetal systemic responses. STUDY DESIGN: Using plasma membranes prepared from the medial layer of fetal aorta, fetal placental artery, and maternal uterine artery obtained between 107 and 134 days of ovine gestation (n = 17), we measured and compared angiotensin II receptor binding density (in femtomoles per milligram of protein) and affinity (in nanomoles per liter) in radioligand binding studies with iodine 125-angiotensin II. Maternal and fetal plasma angiotensin II were also compared. RESULTS: A single class of high-affinity receptor was identified in all arteries. Although the binding density was similar at < 100 and > 130 days for fetal aorta (388 +/- 87 [SE] vs 262 +/- 56), placental artery (319 +/- 95 vs 235 +/- 54), and uterine artery (46 +/- 6 vs 50 +/- 13), values for fetal arteries exceeded those for uterine arteries (p < or = 0.018) in spite of higher fetal plasma angiotensin II (74 +/- 18 vs 30 +/- 8 pg/ml, p < 0.01). Affinity did not differ between arteries and, except for fetal aorta (1.4 +/- 0.2 vs 2.1 +/- 0.4, r = 0.49, p = 0.045), was unchanged during late gestation. CONCLUSION: Differences between fetal and maternal responses and fetal placental and systemic responses to infused angiotensin II in sheep do not reflect alterations in total angiotensin II vascular smooth muscle receptor binding density or affinity.

Angiotensin II↗
PubMed1993

Systemic and uterine responses to chronic infusion of estradiol-17 beta.

Human and ovine pregnancies are associated with increases in plasma levels of estrogens and angiotensin II (ANG II), cardiac output (CO), blood volume (BV), and uterine blood flow (UBF), as well as attenuated ANG II pressor responses. We hypothesized that, in nonpregnant animals, prolonged estradiol-17 beta (E2 beta) treatment would reproduce these endocrine and hemodynamic alterations. Nonpregnant ovariectomized ewes (n = 5) received 5 microgram E2 beta/kg iv followed by 220 micrograms/day for 14 days. Plasma E2 beta increased from 36 +/- 6 to 269 +/- 79 (SE) pg/ml (P < 0.05) during E2 beta treatment, returning to control values 4 days posttreatment. By 3 days of E2 beta, mean arterial pressure (MAP) and systemic vascular resistance (SVR) fell 9 +/- 1 and 29 +/- 1%, whereas heart rate (HR) and CO increased 20 +/- 5 and 26 +/- 1% (P < 0.05). Stroke volume (SV), BV, and plasma volume were unchanged until 7 days of E2 beta, with values rising 17 +/- 5, 13 +/- 3, and 14 +/- 4, respectively (P < 0.05). Although MAP remained similarly depressed (-11 +/- 1%) during week 2 of E2 beta, SVR decreased further (-37 +/- 3%) and was associated with additional increases (P < 0.05) in CO to 44 +/- 5%, reflecting rises in SV (21 +/- 2%) but not HR. Increases in BV correlated with rises in CO (r = 0.55) and SV (r = 0.64) but not HR (r = -0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Myometrial angiotensin II receptor subtypes change during ovine pregnancy.

Although regulation of angiotensin II receptor (AT) binding in vascular and uterine smooth muscle is similar in nonpregnant animals, studies suggest it may differ during pregnancy. We, therefore, examined binding characteristics of myometrial AT receptors in nulliparous (n = 7), pregnant (n = 24, 110-139 d of gestation), and postpartum (n = 21, 5 to > or = 130 d) sheep and compared this to vascular receptor binding. We also determined if changes in myometrial binding reflect alterations in receptor subtype. By using plasma membrane preparations from myometrium and medial layer of abdominal aorta, we determined receptor density and affinity employing radioligand binding; myometrial AT receptor subtypes were assessed by inhibiting [125I]-ANG II binding with subtype-specific antagonists. Compared to nulliparous ewes, myometrial AT receptor density fell approximately 90% during pregnancy (1,486 +/- 167 vs. 130 +/- 16 fmol/mg protein) and returned to nulliparous values > or = 4 wk postpartum; vascular binding was unchanged. Nulliparous myometrium expressed predominantly AT2 receptors (AT1/AT2 congruent to 15%/85%), whereas AT1 receptors predominated during pregnancy (AT1/AT2 congruent to 80%/20%). By 5 d postpartum AT1/AT2 congruent to 40%/60%, and > 4 wk postpartum AT2 receptors again predominated (AT1/AT2 congruent to 15%/85%). In studies of ANG II-induced force generation, myometrium from pregnant ewes (n = 10) demonstrated dose-dependent increases in force (P < 0.001), which were inhibited with an AT1 receptor antagonist. Postpartum myometrial responses were less at doses > or = 10(-9) M (P < 0.05) and unaffected by AT2 receptor antagonists. Vascular and myometrial AT receptor binding are differentially regulated during ovine pregnancy, the latter primarily reflecting decreases in AT2 receptor expression. This is the first description of reversible changes in AT receptor subtype in adult mammals.

Angiotensin II↗
PubMed1993

Calcium modulation of endothelium-derived prostacyclin production in ovine pregnancy.

Refractoriness to angiotensin-II (ANG II)-induced vasoconstriction is greater in the uteroplacental vs. systemic vascular beds during pregnancy, possibly reflecting enhanced uterine artery prostacyclin production. We determined the role(s) of calcium and calcium channels in regulating basal and ANG II-induced vascular prostacyclin production in uterine and omental (systemic) arteries obtained from pregnant (P) and nonpregnant (NP) ewes. To evaluate the endothelial contribution to basal and stimulated prostacyclin production, arteries with and without endothelium also were incubated in the absence and presence of 50 nM ANG II, 5 microM A23187, or 5 microM arachidonate. Basal prostacyclin production by intact and denuded uterine and systemic arteries was P > NP (P < 0.05), plus in intact arteries, production fell approximately 33% in calcium-free Krebs-Henseleit and 5 microM EGTA. Although basal prostacyclin production by P and NP uterine and NP systemic arteries was unaffected by 5 microM verapamil, P systemic artery synthesis fell 41% (P < 0.05). P uterine artery prostacyclin production increased similarly with ANG II (61%) and A23187 (78%) in the presence of calcium (2 mM), whereas NP uterine arteries responded only to A23187 (71%). Verapamil inhibited ANG II-induced increases in prostacyclin synthesis by P uterine arteries. Neither calcium removal nor verapamil altered prostacyclin responses to arachidonate (5 microM). The endothelium accounted for approximately 68% of basal prostacyclin production by all arteries studied and for 100% of ANG II-induced increases by P uterine arteries (P < 0.01). A23187 and arachidonate increased both endothelial and smooth muscle prostacyclin production (P < 0.01). During ovine pregnancy, extracellular calcium entry via activation of potential-gated calcium channels are involved in modulating basal vascular prostacyclin production as well as ANG II-induced increases in uterine artery production. Furthermore, the endothelium is the primary source of basal vascular prostacyclin synthesis and the sole source of ANG II-stimulated increases by uterine arteries during pregnancy.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Reliability of birth certificate reporting of congenital anomalies.

Birth certificates comprise an important source of data on the prevalence of genetic conditions and for monitoring possible teratogens in the population. Investigators have found wide variability (12 to 100%) in the accuracy of reporting. In a large public hospital, of those congenital anomalies detected at birth, only 5.4% were recorded on the birth certificate. This is one of the lowest rates ever reported. An underreporting correction factor may be applied if congenital anomalies are distributed randomly with respect to reporting status, and the rate of reporting is sufficient to comprise a valid sample for estimating a correction factor (that is, 20% or more reported). In this study, factors such as numbers or types of anomalies, race, infant birthweight, or estimated gestational age did not significantly influence the rate of birth certificate reporting. Thus, our data satisfied the first but not the second criterion for derivation of a correction factor. In conducting epidemiologic studies, birth certificate data should be used with: (1) great caution; (2) a system of validation with the medical record to estimate the degree of underreporting and to derive a correction factor; and (3) a priori knowledge that underreporting of congenital anomalies on this document is highly prevalent.

Bias↗
PubMed1992

Vasoconstrictor-induced secretion of ANP in fetal sheep.

Fetal secretion of atrial natriuretic peptide (ANP) increases during volume expansion and hypoxia. It is unknown whether this is associated with alterations in right atrial pressure (RAP) or distension and whether increases in ANP secretion reflect effects of specific vasopressors. To address this we studied fetal sheep (n = 13) at 125-140 days gestation, infusing either angiotensin II (ANG II; 0.023-5.73 micrograms/min) or the alpha-agonist phenylephrine (Phen; 0.031-7.64 micrograms/min) while monitoring mean arterial pressure (MAP), RAP, heart rate, and amniotic sac pressure. Arterial blood was obtained before and at 5 min of infusion to measure ANP, blood gases, and pH; umbilical venous blood was collected to determine placental clearance of ANP. ANG II caused dose-dependent increases in MAP and plasma ANP (P less than 0.05), whereas Phen caused dose-dependent increases in MAP, but ANP rose only with the highest dose (40 +/- 12%). delta MAP and delta RAP were highly correlated for Phen (r = 0.74, P = 0.002) and ANG II (r = 0.90, P less than 0.001), but for both agents the increase in delta RAP was proportionately greater than delta MAP, and increases in plasma ANP were greater per millimeter mercury rise in RAP than that observed with MAP. Increases in ANP were associated with a dose-dependent rise in hematocrit, suggesting decreases in intravascular volume. There was no fetal placental clearance of ANP. As in adults, ANG II- and alpha-agonist-induced fetal ANP secretion appears to primarily reflect increases in RAP and thus right atrial distension.

Angiotensin II↗