HIGH BLOOD PRESSURE associated with sympathetic overactivity is often associated with cardiovascular related mortality and/or morbidity. A therapeutic approach now considered for the treatment of resistant forms of the disease involves the selective denervation of the kidney (16,51,52,57). Kidney function is known to be of primary importance in the long-term regulation and maintenance of arterial pressure (24). However, it is well documented that the autonomic nervous system also plays a critical role in the control of arterial pressure and in the pathogenesis of hypertension (1, 2, 36, 41), especially as it is able to modify renal function (19,29). The autonomic nervous system and kidney are linked through renal nerves that are composed of both efferent sympathetic and afferent sensory fibers (19,29). Although considerable evidence exists suggesting an overexcitation of the sympathetic nervous system in conjunction with neurohormonal factors in the pathogenesis of resistant forms of hypertension, these data do not unequivocally demonstrate whether the effects on arterial pressure following renal denervation are mediated by efferent renal sympathetic nerves or afferent sensory nerves originating in the kidney. This is especially true as afferent signals from the kidney alter the activity of preautonomic neurons in central sites involved in controlling arterial pressure and sympathetic nervous system activity (15), as clearly demonstrated in the article by Xu et al. (50), published in this issue of the American Journal of Physiology-Heart and Circulatory Physiology.Activation of efferent renal sympathetic nerves has been shown to increase renal vascular resistance, renin release, and water reabsorption and decrease sodium ion excretion (19,29). Thus, as expected, denervation of efferent renal sympathetic nerves to the kidney results in reduced renin release and an increase in sodium excretion, but with little change in renal blood flow, perfusion pressure, and glomerular filtration rate (29). On the other hand, sensory nerves originating within the kidney carry information from renal chemoreceptors that detect changes in the composition of the interstitial fluid environment and renal mechanoreceptors which monitor hydrostatic pressure changes within the kidney (35,39,40,47).Renal chemoreceptors have been classified as R1 and R2 by Recordati et al. (39,40). R1 respond to renal ischemia, whereas R2 chemoreceptors are activated by both renal ischemia and changes in the ionic composition of the renal interstitium. R2 chemoreceptors do not respond to changes in arterial pressure but respond in an inverse relationship with a decrease in renal perfusion pressure. This latter group of chemoreceptors has also been suggested to function as renal osmoreceptors (39,40). Furthermore, these renal chemoreceptors have been shown to be activated following intrarenal infusions of substance-P, bradykinin, and adenosine (27, 29 -34). In addition, capsaicin, through activation of the nonselective cation channel transient receptor pote...