The long range objective of this individual program is to provide academic training in Physiology and Neurophysiology, and to formulate research goals consistent with the Candidate's previous clinical background in Maternal-Fetal Medicine. Ultimate objectives include continued pursuit of basic research in an academic setting. Phase I will consist of didactic training, approximately 80%, and 20% research training. Phase II will consist of 80% research effort and 20% didactic effort. Pregnancy is associated with marked changes in intravascular volume, osmolality, and electrolyte balance. Homeostatic control of the renin-angiotensin system is altered with increased angiotensin II (A-II) levels but decreased peripheral pressor response. Hypertensive disorders of pregnancy, preterm labor, and fetal growth retardation are associated with hypovolemia and augmented pressor responses to A-II infusions. Attempts to explain these abnormal responses wholly by renal or adrenal control have been unsuccessful. The means by which peripheral vascular responsiveness is controlled in normal and abnormal pregnancy is unclear. Studies have identified the preoptic area and anterior hypothalamus, PO/AH, as important in the regulation of blood pressure, body water, and temperature. This area contains neurons sensitive to osmotic pressure, A-II, and temperature. It has been shown that in spontaneously hypertensive rats (SHR) Po/AH neurons are significantly larger than in normotensive rats (Wistar-Kyoto,WKY). This suggests that functional differences in PO/AH neuronal sensitivities may exist, which would contribute to neuronal hypertension. Functional differences may also occur in normal and pathologic pregnancies.
The aim of the proposed study is to characterize the sensitivities of PO/AH neurons to osmotic pressure, A-II, and temperature in pregnant and nonpregnant rats; and to compare differences in the sensitivities between WKY and SHR rats. To accomplish this goal, electrophysiological recordings will be conducted in perfused hypothalamic tissue slices taken from age-matched virgin and pregnant WKY rats; and age-matched virgin and pregnant SHR rats. Preoptic neurons will be characterized according to their firing rate responses to changes in osmotic pressure and temperature, as well as to perfusions with media containing A-II or its antagonist, saralasin. Interactions between these factors will be studied; and comparisons made of the various neuronal populations (and their sensitivities) in the pregnant and non-pregnant SHR and WKY animals.
