Atrial natriuretic peptide production and natriuretic peptide receptors in the human uterus and their effect on myometrial relaxation.

OBJECTIVE: The objective of the study was to identify the effect of atrial natriuretic peptide (ANP) on uterine contractility, production of ANP, and natriuretic peptide receptor (NPR) expression in human myometrial tissue. STUDY DESIGN: In an institutional review board-approved study, gravid human myometrium was obtained from patients undergoing cesarean section. Uterine contractility was examined using isometric force tension studies. After regular uterine contractions were obtained with oxytocin, ANP was added in increasing concentrations. ANP concentration was measured from myometrial tissue using radioimmunoassay (RIA). Primary myometrial cell culture was performed and treated with nifedipine vs oxytocin. RIA was performed on these cells and the cell culture media. Western blot analysis was performed on uterine tissue samples for natriuretic peptide receptors. RESULTS: With increasing concentration of ANP (starting at 3 pM), myometrial contraction frequency decreased. ANP was identified in primary cultured myometrial cells and cell culture media. Myometrial ANP concentration increased with advancing gestational age. The concentration of ANP decreased within myometrial cells treated with oxytocin. The amount of ANP in the cell culture media increased from cells treated with nifedipine. Western blot identified NPR-A, -B, and -C in myometrial tissue. NPR-A expression was significantly increased in preterm samples. CONCLUSION: ANP has a dose dependent effect on uterine relaxation. ANP is present in human myometrial cells and appears to be secreted by myometrial cells. The concentration of ANP may vary with gestational age and modulators of uterine contractility. NPR-A, -B, and -C receptor proteins are present in myometrial tissue. NPR-A levels may correlate with gestational age.

The association of hypotonia and depression in the term and near-term neonate with metabolic acidemia.

AIMS: To determine the association of hypotonia and depression in neonates at or near term with metabolic acidemia at birth (umbilical arterial pH<7.0 and base excess <-12 mM). METHODS: This case-control study identified 87 infants without chromosomal or congenital abnormalities born at a single university hospital between 7/91 and 10/04 with hypotonia at birth requiring resuscitation and admission to the neonatal intensive care unit that had a cord gas at delivery. Controls were the subsequent delivery with a cord gas matched by gestational age. RESULTS: Cases and controls did not differ in gestational age (38.7+/-1.9, 38.6+/-1.9 weeks) or birth weight (3,066+/-664, 3,171+/-655 g, P=0.20). Cases were more likely to have a cord pH<7.0 [17 (20%) vs. 1 (1.1%), P=0.0001] and cord pH 7.0-7.1 [13 (14.9%) vs. 2 (2.3%), P=0.003]. Among the hypotonic infants, 31 (35.6%) also were depressed at birth with a 5-min Apgar <7. In the depressed subset of hypotonic neonates 14/31 (45%) had a pH<7.0. Of the 12 hypotonic neonates with seizures, 3 (25%) had pH<7.0. Multivariate analysis showed a significant association between neonatal hypotonia and hypoglycemia, umbilical arterial pH, and nucleated red blood cell count. CONCLUSIONS: Although metabolic acidemia is significantly associated with hypotonia at the time of birth, the majority of neonates with hypotonia and depression or seizures do not have objective evidence of asphyxia as measured by a cord gas at the time of delivery.