Angiotensin II (AII) acts as a growth factor in local systems, mediating diverse effects such as cellular proliferation and apoptosis. These effects are controlled through two main receptor subtypes: AGTR1 and AGTR2. We studied the haplotype frequencies of both receptor genes in women with preeclamptic pregnancies and normotensive pregnant women. We also looked for any association between AGTR1 genotype at sites in the 5' flanking region and binding of AII to platelets, which express AGTR1, in 58 normotensive pregnant women. There were nine common haplotypes of AGTR1, with no significant difference in haplotype frequency between the two groups of women. Platelet AII binding in normotensive pregnant women was associated with the genotype at g.5245C>T in the 5' flanking region of AGTR1 (GenBank AF245699.1), with CC homozygotes at g.5245 having the lowest levels, and g.5245 TT homozygotes having the highest levels (P=0.05). Two novel polymorphisms were identified in AGTR2 (GenBank AY324607.1) at nucleotides g.1701T>C and g.2184A>T. Variation of AGTR2 could be explained by the existence of four common haplotypes. There was evidence for a significant increase in the frequency of the haplotype TAATGC at nucleotides g.1701, g.2041, g.2184, g.4673, g.4679, and g.4975, respectively (P=0.004), in women with preeclampsia.

Large-conductance calcium-activated potassium (BKCa) channels play an important role in the control of myometrial excitability. The aim of the present study was to determine the localization and protein expression of the alpha subunit of BKCa channels in the pregnant and parturient human uterus. An anti-alpha BKCa channel monoclonal antibody (anti-alpha(995-1113)) was used to localize and quantitate immunoreactive BKCa channel protein in myometrium of singleton term pregnant women undergoing either elective (n=26) or emergency Caesarean section following the onset of spontaneous labour (n=25). Data are presented as medians (interquartile range). Differences between groups were analysed using the Mann-Whitney U test. Immunohistochemistry studies localized the alpha subunit of the BKCa channel to the plasma membrane and the cytosol of myometrial cells with similar reaction end product in pregnant women who were or were not undergoing labour. Expression of this subunit, observed as a 125 kDa band in western blots, was significantly higher in pregnant women who were not undergoing labour (30.6% (20.3, 43.9)) than in those who were undergoing labour (15.7% (11.3, 22.4); P<0.01). Reduced BKCa alpha subunit expression in pregnant women during labour may underlie the initiation of uterine contractility during parturition.

Angiotensin-converting enzyme inhibitors are a safe and effective form of treatment for erythrocytosis developing after renal transplantation. The mechanism of action, however, is not mediated by changes in erythropoietin production and remains uncertain.

A considerable body of evidence exists suggesting that the beta(2)-adrenergic receptor (beta(2)-AR) mediates uterine relaxation. However, little information exists on the localization, distribution, or expression of beta(2)-ARs in the human myometrium during the nonpregnant to labor transition. We have used immunochemical methods to investigate beta(2)-AR localization and expression in the nonpregnant, term pregnant, and term parturient uterus. Myometrial biopsies were obtained from 1) nonpregnant, menstruating women undergoing hysterectomy; 2) singleton term pregnant women undergoing elective cesarean section before the onset of labor; or 3) singleton term pregnant women undergoing emergency cesarean section after spontaneous labor. Tissues were processed for immunohistochemistry, immunofluorescence, and Western blotting and a primary polyclonal antibody specific to the human beta(2)-AR to identify immunoreactive myometrial beta(2)-AR. Protein levels were subsequently quantified by densitometry relative to rat brain protein. Immunohistochemistry and immunofluorescence demonstrated the presence of beta(2)-AR predominantly at the plasma membrane and also in the cytosol of myometrial cells. A 2-fold decrease in protein levels of the beta(2)-AR was apparent in the myometrium of labor compared with that of nonpregnant and pregnant nonlaboring women (P < 0.05). These results demonstrate that down-regulation of beta(2)-AR protein with labor may constitute a contributory mechanism by which uterine quiescence is removed at term.