It has long been known that the adult circulation is controlled by interplay among neural and local tissue mechanisms. But a largely unsolved question is when during postnatal development does each mechanism before effective. Differences in the time-course of postnatal development of the peripheral neural vasoconstrictor and local vasodilator systems in the regulation of blood flow are being investigated in anesthetized swine of various ages. Both physiologic and pharmacologic approaches are used. Arterial pressure is registered by strain gauge transducer, and flow by non-cannulating electromagnetic transducer. Three vascular beds have been selected for study. The role of neural activity is assessed in experiments involving denervation and stimulation of sympathetic efferent fibers. Autoregulatory control is assessed by step-changes in perfusion pressure via compression of the aorta below the diaphragm to provide immediate and delayed changes in vascular resistance as evidence for the presence and range of blood flow autoregulation. Experiments on the renal and femoral circulations have been completed. Ongoing research on the intestinal circulation has progressed to include experiments comparing the ileal and jejunal vascular beds, which provide blood to intestinal segments having somewhat different transport functions. In the proposed continuation of this investigation, controlled-pressure protocols will be carried out, responses to postganglionic sympathetic denervation and nerve stimulation will be determined, and responses to single injections and continuous infusion i.a. of vasoactive compounds will be evaluated. The effects of the latter will be assessed in terms of alterations in perfusion pressure during controlled-flow perfusion of ileal and jejunal segments, and of """"""""autoregulatory escape."""""""" In both the ongoing and new experiments, differences between neurally and locally mediated responses will be examined at each age by statistical analysis of the incidence and magnitude of effects, and differences between age groups will be sought. The long-term goal to examine regional circulatory responses during physiologic stress will then be regional blood flow distribution (among kidney, hindlimb, and ileum or jejunum) and blood flow autoregulation during experimentally induced in creases in the local demand for blood flow, by increasing skeletal muscle work or intestinal activity.
