The experiments presented in this proposal are the beginning of a long series of studies designed to investigate the role of spinal systems in the regulation of cardiovascular function. A major impetus for these studies is that approximately 12,000 Americans are rendered paraplegic or quadriplegic each year. These patients exhibit a variety of cardiovascular complications, including the sometimes fatal """"""""hypertensive crisis"""""""" which is mediated by spinal pathways. Most of the current knowledge in this area comes from acute neurophysiological studies in anesthetized animals. Presented in this proposal are experiments in conscious rats with chronic spinal lesions, which will examine the functional role of spinal networks in the physiology and pathology of cardiovascular regulation in paraplegia. It is hypothesized that basal levels of arterial pressure in spinal rats are dependent on chronically elevated renal nerve activity. This hypothesis will be tested by determining the effects of renal denervation and beta-adrenergic blockade on body fluid balance and long-term arterial pressure regulation in spinal rats. Finally, experiments will be conducted to establish the existence of tonic sympathetic vasoconstrictor activity in spinal rats. Preliminary studies in conscious spinal rats have revealed a marked lability of arterial pressure. The hemodynamic basis for this lability will be investigated by measuring arterial and central venous pressures, and regional vascular resistances using chronically implanted catheters and Doppler flow probes. Specifically, these studies will determine the relative contributions of somatic motor spasms and spontaneous discharges of spinal sympathetic activity to the lability of arterial pressure . The role of somatic and visceral afferents, from various spinal levels, in evoking a """"""""hypertensive crisis"""""""" will be studied. The specific efferent response patterns (regional hemodynamics) to these stimuli will be characterized to establish the role of both efferent skeletal and autonomic pathways in mediating the hypertensive crisis.
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