The role of renal sympathetic nerve activity in mediating renal hemodynamic alterations in rat models of renal impairment

Background. It is well known that the pathogenesis of most renal diseases is associated with alterations in renal hemodynamics and also that the regulation of renal hemodynamics is under the direct control of renal sympathetic nerve activity. Objectives. The role of the renal sympathetic nervous system in the early deterioration of renal hemodynamics in rats with pathophysiological states of renal impairment was investigated. Material and Methods. Male Sprague Dawley rats were induced with acute renal failure or diabetes mellitus by cisplatin or streptozotocin (STZ), respectively. Cisplatin-induced renal failure was confirmed by impaired renal function and the diabetic state and early renal impairment were confirmed by hyperglycemia, changes in physiological parameters, and renal function. The hemodynamic study was conducted on anesthetized rats 7 days after cisplatin or STZ administration. During the acute study the renal sympathetic nerves were electrically stimulated at increasing frequencies and the responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Results. In the innervated rats with renal impairment, renal nerve stimulation (RNS) caused significant attenuation (all P < 0.05 vs. innervated control) of the renal vasoconstrictor responses. These responses were markedly (all P < 0.05) abolished when renal denervation was performed; however, they appeared significantly (all P < 0.05) higher than the denervated control counterparts. Conclusions. The findings strongly suggest an early involvement of renal sympathetic nerve action in the pathogenesis of renal impairment accompanying renal failure and diabetes. The data further suggest an early enhancement of renal sensitivity to intrarenal norepinephrine upon the removal of renal sympathetic tone by denervation.