The transition from fetal to newborn life is associated with numerous physiological adjustments which are achieved through interacting neural and hormonal mechanisms. With delivery at term, there are striking increases in the activity of the renin-angiotensin system and sympathetic outflow. However, with premature delivery, the sympathoexcitatory response is absent while cardiovascular and metabolic functions are impaired. Recently, the use of antenatal glucocorticoids in preterm labor to promote fetal lung maturity has been shown to improve cardiovascular responses at birth and stimulate sympathetic nerve activity, although the mechanisms regulating these responses are not known. In adults, anatomic, physiologic and biochemical studies have implicated the paraventricular nucleus (PVN) of the hypothalamus in cardiovascular regulation, being a major source of forebrain input to the sympathetic nervous system and an important link in coupling in the renin-angiotensin system with central autonomic regulation. Based on these studies, we are postulating that the PVN functions as an important regulator of sympathetic activity at birth and that developmental changes in angiotensin II type I (AT1) receptor expression and function within the PVN mediate these sympathetic responses. To test this hypothesis, the present proposal is designed to a) elucidate the physiological role of the PVN in regulating cardiovascular and sympathetic function at birth, b) to determine the influence of maturational changes in brain AT1 receptors on central autonomic function and c) investigate whether the PVN and central AT1 receptors participate in glucocorticoid augmentation of the sympathoexcitatory response at birth. These studies will improve our understanding of how the developing fetus and newborn infant regulate sympathetic outflow, increase our knowledge about cardiovascular function early in life and may lead to the development of new therapeutic strategies to prevent morbidity and mortality related to alterations in systemic hemodynamics.
| Segar, Jeffrey L; Van Natta, Timothy; Smith, Oliva J (2002) Effects of fetal ovine adrenalectomy on sympathetic and baroreflex responses at birth. Am J Physiol Regul Integr Comp Physiol 283:R460-7 |
| Segar, Jeffrey L; Ellsbury, Dan L; Smith, Oliva M (2002) Inhibition of sympathetic responses at birth in sheep by lesion of the paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol 283:R1395-403 |
| Segar, J L; Bedell, K A; Smith, O J (2001) Glucocorticoid modulation of cardiovascular and autonomic function in preterm lambs: role of ANG II. Am J Physiol Regul Integr Comp Physiol 280:R646-54 |
