Relaxin and drinking in pregnant rats

Work reported in this chapter describes the potential role of relaxin in resetting cardiovascular thresholds in pregnant rats. Relaxin, a polypeptide produced primarily by the ovary in pregnant animals in many species, is also produced in the brain. Exogenous administration of relaxin into the brain causes a profound drinking response which is negated by pretreatment with a specific monoclonal antibody to rat relaxin when the antibody is injected into the brain. Neutralizing the action of endogenous brain relaxin in pregnant rats also blocks the normal increase in drinking that is observed in rats at night during the second half of pregnancy. Relaxin acts through the forebrain angiotensin system at the level of the subfornical organ (an important interface between the blood, the brain and the cerebrospinal fluid) as blockade of the angiotensin II receptor action negates several central actions of relaxin. Expression of angiotensin II AT1 receptors in the subfornical organ increases in parallel with the increase in circulating relaxin seen in the second half of pregnancy. Neutralizing the effects of endogenous brain relaxin, using central injections of the monoclonal antibody, blocks this increase in the expression of angiotensin II AT1 receptors in subfornical organ. These data imply that relaxin in the brain may act to affect central cardiovascular thresholds in rats and this may be important for the normal physiology of pregnancy

The dipsogenic effects of rat relaxin: The effect of photoperiod and the potential role of relaxin on drinking in pregnancy

Experiments were done to examine whether rat relaxin is dipsogenic and whether such dipsogenic effects of rat relaxin are related to time of injection during the light-dark cycle. Female rats were fitted with a chronic intra-cerebro-ventricular (icy) cannula. Rat relaxin (2.5, 5, 10, 25, 50, or 100 ng/2 μl in 0.9% saline) was injected into the right lateral ventricle at either morning (0800-1000 h), afternoon (1400-1600 h), or night (2200-2400 h), and water consumption was measured. Relaxin caused a dose-dependent dipsogenesis at doses ≥ 5 ng, but the sensitivity and magnitude of the response varied with the photoperiod. Water consumption was smallest (3.5 ± 0.7 ml at 50 ng) and least sensitive (minimal effective dose at 25 ng) in the afternoon and maximal (17.7 ± 2.3 ml at 50 ng) and most sensitive (minimal effective dose 5 ng) at night. The latency from injection to drinking was 55.8 ± 10.4 sec (mean ± SEM) and did not vary significantly with either the dose or time of day. A second set of experiments was done to examine the effects of neutralizing the central actions of relaxin on drinking behavior in pregnancy. Pregnant rats were injected daily, through a chronically implanted icv cannula, with either a specific monoclonal antibody raised against rat relaxin from day 12 to day 22 of gestation or with saline as a control. Drinking and eating behavior and weight gain were monitored every 12 h during pregnancy. There was a significant decrease in water consumed at night, but no effect on drinking during the day in relaxin-neutralized rats. These animals also showed a decrease in weight gain during pregnancy compared with controls and gave birth to lighter-weight litters. These data provide evidence that the dipsogenic response to exogenous rat relaxin in female rats varies with time of injection during the light-dark cycle and suggest that relaxin in the brain may have a role in nighttime drinking behavior during the second half of pregnancy