Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy.

Abstract

To investigate the degree to which endogenous increases in estradiol (E2) and progesterone (P4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for in vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were followed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E2 increased 10-fold, PRA increased 2-fold, and absolute levels of E2 and P4 were positively correlated (r = 0.63; P < 0.05). After ovulation, which was induced by hCG, E2 fell by 50% (day 7), but there was a 50-fold increase in P4 and a further 5-fold increase in PRA. By day 14, E2 increased again in the women who conceived, to levels even higher than those in the follicular phase, and both P4 and PRA increased 2- to 3-fold between days 7 and 14. In contrast, E2, P4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E2, P4, and PRA remained very high in the pregnant women [E2, 2297 +/- 255 pg/mL (8430 pmol/L); P4, 103 +/- 22 pg/mL (328 pmol/L); PRA, 33 +/- 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pregnancy, there was a positive relationship between PRA and P4 (r = 0.68; P < 0.05). There was also a positive relationship between PRA and E2 (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E2 level. Like renin, urinary aldosterone excretion (UA) increased 5-fold during the luteal phase (day 7) and by a further 3-fold between days 7 and 21 in the pregnant women, reaching very high levels [135 +/- 28 micrograms/day (375 nmol/day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). Plasma angiotensinogen increased from 2146 +/- 283 ng angiotensin-I/mL (n = 8) to 3682 +/- 607 (n = 8) on day 7 and to 5353 +/- 799 (n = 3) on day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldosterone. There was no hypokalemia. These results demonstrate marked increases in plasma renin and UA in coordination with increases in plasma E2 and P4 during ovarian stimulation and early pregnancy, and coordinated falls during luteolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Factors correlated with plasma renin activity in general Japanese population

“…In our study, the blood sampling in sitting position after being ambulatory for hours might further enhance the difference. It has been reported that sex hormone might be involved in high PRA [25,26]. Smoking is thought to be an inducer of renin secretion by increasing sympathetic activity.…”

Vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion and improve glucose tolerance in female rats

“…Hence many diabetic patients are treated with ACE inhibitors or Ang II receptor antagonists for hypertension or as part of a renal protection strategy. It has became clear that oestrogen can influence RAS [41][42][43][44][45][46][47] and that this effect is mediated by down-regulating renin, ACE and Ang II receptor expression [48]. An interesting review has reported that gender and sex hormones affect the components of RAS by multifarious mechanisms [9].…”

Effects of gender on the renin-Angiotensin system, blood pressure, and renal function

“…Sealey et al [4] studied women undergoing ovarian stimulation for fertilization and found that PRA and urinary excretion of aldosterone were significantly increased during the luteal phase of the menstrual cycle, when plasma estrogen levels are highest, compared with other phases. Furthermore, a significant positive correlation existed between levels of these RAS components and estrogen.…”

“…Given the key role of the renin-angiotensin system (RAS) in the pathogenesis of hypertension, cardiovascular disease, and chronic renal disease, gender differences in RAS function have received increasing attention. Studies of the impact of gender on the RAS have provided conflicting results, with groups suggesting that the system is activated [3,4] or suppressed [5] in women compared with men. Most studies in humans examining the relationship between gender, estrogen status, and the RAS have been limited by reliance on baseline measurements of components of the system.…”