Nitric oxide synthase activity and expression are decreased in the paraventricular nucleus of pregnant rats

Pregnancy is characterized by elevated heart rate and decreased total peripheral resistance and arterial blood pressure. Plasma volume is expanded and plasma osmolality is decreased, yet vasopressin secretion in pregnant animals, including humans, is no different than levels in the nonpregnant state. Although reflex compensatory sympathoexcitation is suppressed, baseline sympathetic nerve activity to the heart and vasculature is well maintained or slightly elevated in pregnancy. Clearly there are central nervous system (CNS) adaptations in systems for regulation of cardiovascular and body fluid homeostasis in pregnant animals. The paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus are important CNS sites for control of sympathetic nerve activity and vasopressin secretion. Nitric oxide (NO), an important neuromodulator in these hypothalamic nuclei, contributes to tonic inhibition of neurosecretory and pre-autonomic neurons. Alterations in NO within the PVN and SON could contribute to changes in regulation of vasopressin and sympathetic nerve activity in pregnancy. In the present study, nitric oxide synthase (NOS) activity (NADPH-diaphorase staining), neuronal NOS (nNOS) protein, and nNOS mRNA were assessed in nonpregnant estrus stage and near-term pregnant rats. nNOS mRNA, protein, and activity were greater in the PVN than in the SON. In the PVN only, pregnancy was associated with significant decreases in all three measurements for assessment of nNOS. Thus decreased NO production and relative disinhibition of the PVN may contribute to maintenance of baseline vasopressin secretion and baseline sympathetic nerve activity in the pregnant state.