Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium

© 2016 Society for Reproduction and Fertility.Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥2.0-fold change with false discovery rate be

Dietary salt modifies the blood pressure response to renin-angiotensin inhibition in experimental chronic kidney disease

Chronic kidney disease contributes to hypertension, but the mechanisms are incompletely understood. To address this, we applied the 5/6th nephrectomy rat model to characterize hypertension and the response to dietary salt and renin-Angiotensin inhibition. 5/6th nephrectomy caused low-renin, salt-sensitive hypertension with hyperkalemia and unsuppressed aldosterone. Compared with sham rats, 5/6th nephrectomized rats had lower Na/H exchanger isoform 3, Na-K-2Cl cotransporter, Na-Cl cotransporter, a-epithelial Na channel (ENaC), and Kir4.1 levels but higher serum and glucocorticoid-regulated kinase 1, prostasin, c-ENaC, and Kir5.1 levels. These differences correlated with plasma renin, aldosterone, and/or K. On a normal-salt diet, adrenalectomy (0 ± 9 mmHg) and spironolactone (11 ± 10 mmHg) prevented a progressive rise in blood pressure (10 ± 8 mmHg), and this was enhanced in combination with losartan (41 ± 12 and 43 ± 9 mmHg). A high-salt diet caused skin Na and water accumulation and aggravated hypertension that could only be attenuated by spironolactone (16 ± 7 mmHg) and in which the additive effect of losartan was lost. Spironolactone also increased natriuresis, reduced skin water accumulation, and restored vasorelaxation. In summary, in the 5/6th nephrectomy rat chronic kidney disease model, salt-sensitive hypertension develops with a selective increase in c-ENaC and despite appropriate transporter adaptations to low renin and hyperkalemia. With a normal-salt diet, hypertension in 5/6th nephrectomy depends on angiotensin II and aldosterone, whereas a high-salt diet causes more severe hypertension mediated through the mineralocorticoid receptor. NEW and NOTEWORTHY Chronic kidney disease (CKD) causes salt-sensitive hypertension, but the interactions between dietary salt and the renin-Angiotensin system are incompletely understood. In rats with CKD on a normal-salt diet targeting aldosterone, the mineralocorticoid receptor (MR) and especially angiotensin II reduced blood pressure. On a high-salt diet, however, only MR blockade attenuated hypertension. These results reiterate the importance of dietary salt restriction to maintain renin-Angiotensin system inhibitor efficacy and specify the MR as a target in CKD