Our research has shown that the baroreflexes govern the lability, but not the mean level of arterial blood pressure. Therefore, the activity of certain brainstem areas may determine the mean level of arterial pressure and may participate in baroreflex regulation of the lability of arterial pressure as well. This proposal is designed to examine the participation of four of these areas: 1) the A1 cells of the ventrolateral medulla, 2) the C1 cell group of the rostral ventrolateral medulla, 3) the A5 cell group of the ventral pontomedullary junction, and 4) the paraventricular and supraoptic nuclei of the hypothalamus. Four projects are proposed and each examines one of these areas by utilizing the same experimental design. Four groups of rats are studied. The baroreflexes are abolished by sinoaortic denervation (SAD) in two of these groups. Then, chemical lesions are placed in one of the four brainstem areas in the first SAD group and sham-lesions are made in the same area in the second SAD group. A third and fourth group serve as sham-SAD controls. Lesions are placed in the selected areas in the first sham-SAD group and sham-lesions are made in the second sham-SAD group. Basal cardiovascular levels are monitored and baroreflex function tested. The relative contributions of three major pressor systems in establishing the mean level of arterial pressure is assessed from assays of plasma catecholamines, vasopressin, and renin activity before and after selective blockage of each of these systems. Then arterial pressure is elevated to hypertensive levels by the use of a behavioral-stress paradigm and the plasma levels of these hormones are determined again. Finally, the responsiveness of these pressor systems to drugs that centrally raise or lower sympathetic activity is assessed. The objectives of this proposal are: 1) to study the role of selected brainstem areas in establishing the mean level of arterial pressure, 2) to determine whether these areas also participate in baroreflex regulation of the lability of arterial pressure, 3) to discover the relative contributions of three major pressor systems to the mean level and lability of arterial pressure, 4) to re-examine the role of these brainstem areas and the pressor systems in regulating the circulation after arterial pressure is raised to hypertensive levels, and 5) to examine possible alterations in the responsiveness of these pressor systems due to SAD and/or lesion of these areas when sympathetic activity is altered by centrally-acting drugs.
