Spinally projecting and vasopressin containing cells in the hypothalamic paraventricular nucleus of female rats are activated by relaxin in the forebrain circulation

Abstract

In pregnancy, blood volume and baseline sympathetic nerve activity are increased, while baseline arterial blood pressure is slightly decreased. Relaxin, an ovarian hormone which is secreted in pregnancy, activates the subfornical organ, a circumventricular organ, and regions within the brain parenchyma which are associated with control of blood volume and sympathetic nerve activity. The current experiments phenotyped cells in the paraventricular nucleus of the hypothalamus which are activated by relaxin. Carotid and femoral artery and femoral vein catheters were implanted in female virgin rats. Spinally projecting cells were retrogradely labeled by microinjection of fluorogold or cholera toxin-b (CTb) (90 nl) into the intermediolateral cell column. After 5 days human relaxin-2 (1 μg/h) or saline (1 ml/h) was infused (1.5 h) into the forebrain circulation (intra-carotid artery, ica) of conscious rats. Relaxin (n=5) resulted in a modest increase in mean arterial pressure (+7±1 mm Hg) while saline (n=5) had no effect (+1±1 mm Hg). Rats were deeply anesthetized, transcardially perfused with 4% paraformaldehyde, brains sectioned (35 μm), and Fos-, CTb-, and vasopressin (VP-) immunoreactivity (IR) were evaluated. Following relaxin, cells in the lateral margins of the subfornical organ expressed Fos-IR, consistent with activation of neurons which project to the paraventricular nucleus. Overall 23% of VP-IR cells and 20% of spinally projecting cells were activated (Fos-IR) by ica relaxin. In contrast, co-labeling with Fos was minimal in saline treated rats. These data provide an anatomical substrate for a role of relaxin in the adaptations in regulation of vasopressin and sympathetic nerve activity in pregnancy. HL091164(CMH).