Relaxin alters the plasma osmolality-arginine vasopressin relationship in the rat

Abstract

During pregnancy, in women and the rat, there is a resetting of the plasma osmolality-arginine vasopressin relationship (P(osmol)/PAVP) such that a decrease in P(osmol) is maintained without suppression of PAVP. This occurs at a time when relaxin is detectable in plasma. The hypothesis tested here was that relaxin could alter the P(osmol)/PAVP in the non-pregnant rat. One group of ovariectomized rats (n = 15) was treated for 7 days with intravenous synthetic human relaxin (10 micrograms/h) in 10 microliters 0.9% (w/v) NaCl. Controls were two groups of rats either with no treatment (n = 15) or treated with vehicle alone (n = 15). One-third of each group received hypertonic saline (0.4 mol NaCl/l, 2 ml/100 g body weight i.p.) on day 7, and one-third were deprived of water for the final 24 h. All rats were killed by decapitation and blood was collected rapidly (< 40 s) for hormone and osmolality assays. The P(osmol) in all relaxin-treated rats was significantly (P < 0.001) lower than that in both control groups, but the PAVP was unchanged. The log PAVP/P(osmol) regression line was significantly shifted in elevation (P < 0.001) but not in slope. Thus treatment of ovariectomized rats with relaxin caused changes in fluid balance which mimic those occurring in normal pregnancy.

Effects of relaxin, pregnancy and parturition on collagen metabolism in the rat pubic symphysis

“…In addition, the observed changes in the extracellular matrix were associated with increased tissue water content during normal gestation, which reflected the overall hypotonicity of pregnancy and did not occur in ovariectomised animals treated with oestrogen and progesterone only. However, as the administration of relaxin to ovariectomised animals induced a significant decrease in tissue wet and dry weight, without significantly altering tissue water content, these data do not support the earlier proposal that relaxin is responsible for the changes in fluid balance observed during pregnancy (Weisinger et al 1993). The significant decrease in collagen levels during pregnancy and parturition coincide with a rapid increase in serum relaxin levels during this time in the rat (Sherwood & Crnekovic 1979, Sherwood et al 1980, which suggests that the secreted hormone may play a significant role in remodelling collagen levels in preparation for parturition.…”

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat

“…Evidence that relaxin [together with other hormones such as angiotensin II (Ang II) and vasopressin] plays a physiological role in regulating body fluid homeostasis during pregnancy is that passive immunization with centrally administered antibodies raised against rat relaxin reduces water drinking in pregnant rats (14), and that chronic i.v. infusion of relaxin in ovariectomized rats results in hyponatremia, mimicking the hyponatremia that occurs in pregnant animals and humans (15).…”

Relaxin is a potent renal vasodilator in conscious rats

“…Circulating RLX concentrations of 20-40 ng/ml have been measured in rats of 12-14 gestational days (19). Based on previous work (14,25), an infusion rate of 4 µg/h for purified porcine RLX or rhRLX would be expected to produce plasma levels of 20-40 ng/ml. In fact, we reached this target level; see Results.…”

“…Third, the gestational rise in RLX corresponds with another early physiological adaptation in human pregnancy, namely, osmoregulatory changes (13). Chronic administration of recombinant human RLX 2 (rhRLX) to ovariectomized rats reduced plasma osmolality and the osmotic threshold for arginine vasopressin release to levels comparable to the gravid condition (14). Fourth, the osmoregulatory changes of pregnancy were mimicked by administering hCG to women in the luteal phase of the menstrual cycle and intact female rats, but not to men or ovariectomized rats, suggesting the intermediary role of an ovarian hormone (15)(16)(17).…”