Afferent renal nerves (ARN) have been implicated in the control of arterial pressure, fluid balance and the intense pain due to ureteral obstruction. Electrical stimulation of ARN elicits reflex changes in arterial pressure and sympathetic hypertension in rats. Mechanical or chemical stimuli activate specific populations of ARN fibers with corresponding changes in efferent sympathetic nerve activity. The mechanisms by which ARN input affects autonomic function are unknown. The goals of this proposal are to determine the spinal and supraspinal projections of modality-specific ARN input, the central connections of these neurons, the nature and extent to which ARN input is modulated and the relationship between ARN input and sympathetic, hemodynamic and behavioral activity. The majority of the studies will require the identification of single spinal gray neurons responding to ARN stimulation. The relationship between ARN input and sympathetic nerve activity will be done by comparing the spontaneous activity of these neurons to splanchnic nerve discharge using the technique of spike-triggered averaging. The results of this study will identify how closely ARN activity is coupled to sympathetic nerve activity to better define reno-visceral reflexes. The pathway and termination fields of ascending projections from these neurons will be determined by antidromically activating cells from supraspinal sites. Responses of spinal gray cells to specific chemical and mechanical stimulation of the kidney will also be determined to identify sites responsive to specific stimulus modalities and to try to interpret their role in spinal and supraspinal reflexes. Tonic descending modulation of ARN input will be studied by comparing responses to ARN stimulation before and after cold block of the cervical spinal cord. Phasic modulation will be examined by identifying sites in the brain from which stimulation-induced facilitation or inhibition of responses to ARN stimulation can be elicited. Collateral modulation and interactions with baroreceptor afferents will also be investigated. Results from these studies will elucidate the extent, nature and sources of descending modulatory influences to clarify their role in conduction of renal afferent input. Finally, the hemodynamic and behavioral effects of ARN stimulation will be observed in awake, freely moving rats to determine the extent to which ARN are involved in the regulation of arterial pressure, fluid balance and visceral pain. These studies are designed to clarify the functional and anatomical projections of ARN in order to better understand their role in normal and pathological states.
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