Plasma volume expands by approximately 50% in normal pregnancy. This is a critical adjustment of pregnancy since a reduced blood volume is directly correlated with preeclampsia still a major cause of maternal death, and with fetal growth retardation. The mechanism by which volume expands during pregnancy is not yet defined, in spite of well described volume regulatory mechanisms in male animals. Plasma volume in the nonpregnant animal is controlled by receptors in the heart, known collectively as cardiac receptors, which respond to increased blood volume by activating a neural reflex pathway with afferent fibers in the vagus nerve, central connections in the brainstem, and efferent outflow primarily to the kidney, where sympathetic nerve activity is reduced evoking fluid loss and lowering blood pressure. Evidence suggests that the sensitivity of this reflex is reduced in pregnancy such that stretch of cardiac receptors elicits smaller reflex effects. This may be an important alteration which allows the large expansion of blood volume without reflex fluid loss which would occur in the nonpregnant animal. This study will test the hypothesis that cardiac receptor activity measured in single afferent fibers of the vagus nerve, is reduced in pregnant compared to virgin rats. Cardiac receptors in deeply anesthetized rats (n=20/group) will be activated mechanically, by injecting graded volumes of saline into the right atrium or by inflation of an atrial balloon, and chemically, using graded doses of intra-atrial phenylbiguanide. Responses to these stimuli will be measured in discharge activity of single cardiac receptor afferent fibers blood pressure, and renal sympathetic nerve activity. These techniques will be used to characterize: 1) the threshold stimulus (volume of saline or balloon and dose of phenylbiguanide) for an increase in cardiac receptor firing, and the sensitivity of the stimulus/response relationship (how cardiac receptor afferent discharge increases for an increase in stimulus intensity), 2) the gestational age at which the reduction in reflex sensitivity can be measured (i.e. early in pregnancy when blood volume is not yet expanded or in late gestation when expansion is maximal), and 3) the effect of changes in afferent cardiac receptor activity on the blunted reflex changes in efferent renal sympathetic nerve activity and blood pressure (total reflex gain). It is anticipated that the results will contribute significantly to the overall goal of elucidating mechanisms for alterations in neural control of the circulation during pregnancy. The identification of specific mechanisms which initiate and maintain an expanded blood volume during pregnancy has important clinical implications for nursing management of the pregnant woman by describing the physiologic changes which underlie critical clinical observations and therapeutic modalities involved in prevention and treatment of preeclampsia and intrauterine growth retardation.
