HYPOTHALAMIC CONTROL OF VENOUS CAPACITANCE

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There is considerable evidence that sympathetic nervous system control of venous capacitance plays an important role in cardiovascular homeostasis. Similarly, a good deal of evidence indicates that the central nervous system (CNS) controls sympathetic outflow to the cardiovascular system. However, there is relatively little data directly investigating CNS control of venous function. The proposed research is designed to test the hypothesis that the paraventricular nucleus of the hypothalamus (PVN) plays an important role in the control of venous function. The effects of the PVN on venous function will be studied at three levels; whole conscious animals, isolated vascular beds and individual microvenules. The goals of the proposal will be to: 1) determine if activation of the paraventricular nucleus of the hypothalamus (PVN) influences mean circulatory filling pressure (MCFP) and the systemic pressure-volume relationship in the conscious rat, 2) characterize the hemodynamic mechanisms involved in these responses, 3) characterize the neural and humoral effector mechanisms involved, 4) determine the regional vascular bed (splanchnic versus skeletal muscle) capacitance responses and the mechanisms involved in these responses, and 5) determine the effects of PVN stimulation on the pressure-diameter relationships in individual veins in the splanchnic and skeletal muscle vascular beds. These goals will be met by measuring arterial and venous blood pressures, cardiac output and regional blood flow. In conscious rats, MCFP will be used as an index of venous tone and will be calculated from the arterial and venous pressures following a brief interruption of cardiac output. MCFP-blood volume curves will be constructed to analyze the systemic pressure-volume relationship. MCFP will be determined during activation of the PVN before and after surgical (e.g., adrenal medullectomy) and pharmacological (e.g., alpha adrenoreceptor blockade) interventions. In vivo constant-flow perfused vascular bed preparations will be used to determine the regional venous capacitance responses and determine the hemodynamic mechanisms that contribute to the venous capacitance effects of PVN activation. Finally, direct measurement of microvenular pressures and diameters will be carried out using servo-null pressure measurements and in vivo microscopy to assess the effect of PVN stimulation on the pressure-volume relationships in individual veins. The proposed research uses a multifaceted approach to systematically study the functional role of the PVN in the control of venous capacitance at three levels of vascular organization. These studies will provide meaningful new information regarding CNS control of venous function. This information is clinically relevant since venous function is altered in human hypertensives and certain centrally acting antihypertensive drugs (e.g., clonidine) may influence venous capacitance. In addition, the venous system participates in the cardiovascular responses to stress, however, the CNS sites and mechanisms involved remain to be elucidated. The proposed studies will provide important background data for future studies aimed at addressing these questions.