NEURAL CONTROL OF THE CIRCULATION IN PREGNANCY

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In both humans and most animal models (including the rat), normal pregnancy is characterized by increased blood volume and cardiac output, and decreased arterial blood pressure and total peripheral resistance. Renin and prostanoid synthesis are increased during pregnancy. Interestingly, pregnancy is associated with decreased pressor responsiveness to exogenously administered pressor agents: an effect which is reversed following blockade of prostaglandin synthesis. Obviously, major alterations in the neural-humoral control of the circulation would be necessary to accommodate the hemodynamic profile of normal pregnancy. However, few studies exist in which cardiovascular reflex mechanisms have been examined in pregnancy. The overall goal of the current proposal is to test the general hypothesis that during pregnancy adaptations occur in the neural control of the circulation at the level of the baroreceptors, the central nervous system and the peripheral vasculature which contribute to the hemodynamic profile characteristic of normal pregnancy. These adaptations could be related to the changes in blood volume, prostanoid production, and/or changes in the interaction between reflex systems. Experiments are planned in three groups of rats - nonpregnant, midterm-pregnant (progesterone dominant), and late-pregnant (estrogen dominant) - and comparisons will be made to determine the effects of pregnancy on: 1.) single unit afferent arterial baroreceptor discharge and the effects of blockade of prostanoid synthesis; 2.) arterial and cardiopulmonary baroreflex control of efferent regional sympathetic nerve activity and both the volume and chemical (prostanoids) sensitivity of cardiopulmonary receptors; 3.) parasympathetic and sympathetic components of reflex control of heart rate; 4.) baroreflex control of uterine vascular resistance and efferent sympathetic nerve activity to the uterus; and 5.) efferent responses to activation of cardiovascular related central nervous system sites. These experiments will yield new information on possible mechanisms for the cardiovascular adaptations of pregnancy. In addition, since failure of the normal adaptations is associated with serious pathological states such as pregnancy-induced hypertension, these studies will provide valuable clinically applicable information.