4 further rise in BP and NE secretion from the PH of CKD rats. Third, the administration of an anti-rat IL-1β antibody decreases NOS mRNA expression in the several brain nuclei (PH, locus coeruleus, and paraventricular nuclei) of both control and CKD rats. Finally, in CKD rats we observed an increase in the abundance of IL-1β mRNA in all brain nuclei tested. In all, these ﬁndings suggest that IL-1β modulates the activity of the SNS via activation of neuronal NOS and partially mitigates the rise in BP and SNS activity in CKD as well as in control rats. 3.6. Treatment of Resistant Hypertension with Antiadrenergic Agents. Given the evidence for the role of the sympathetic nervous system in hypertension, antiadrenergic agents may be considered in the treatment of hypertension, especially in the setting of diﬃcult to control BP. The numerous antihy- pertensive agents that have become available over the last few decades have overshadowed the potential of centrally acting agents such as clonidine and guanfacine in conventional antihypertensive therapy. However, experimental evidence has demonstrated the ability for these agents to decrease peripheral SNS activity and BP. For example, in salt-sensitive SHR, intrahypothalamic infusion of clonidine abolished the hypertensive eﬀect of dietary salt supplementation and decreased the salt-related increase in plasma NE seen in control rats supplemented with dietary salt [57]. In operative candidates, clonidine administration has been shown to decrease plasma NE levels typically associated with the stress of surgery in comparison to placebo [58]. We were the ﬁrst to demonstrate that clonidine administration reduced SNS activity and caused natriuresis in salt-sensitive patients with essential hyperitension [59] and in patients with chronic kidney disease [60, 61]. Further studies are needed in the setting of resistant hypertension to determine the eﬃcacy of antiadrenergic agents. 3.7. Catheter-Based Renal Denervation for the Treatment of Resistant Hypertension. New advances in technology recently have brought about the translation of basic science ani- mal models of therapy for resistant hypertension into the forefront of current therapy for resistant hypertension. A recent case report by Schlaich et al. describes a 59-year- old patient on seven antihypertensive medications who underwent renal sympathetic ablation of the aﬀerent renal nerves, which resulted in a BP reduction to 127/81 mg Hg from a baseline blood pressure of 161/107 mm Hg over a twelve-month period [62]. A concomitant reduction of total body norepinephrine spillover and plasma renin was noted. A multicenter study involving 40 patients with resistant hypertension on an average of four or more antihypertensive medications who underwent ablation of the renal sympa- thetic aﬀerent and eﬀerent nerves was recently published [63]. An average BP reduction of 27 mm Hg systolic and 17 mm Hg diastolic was achieved, although the authors do clarify that BP medications were adjusted and in some patients, uptitrated after renal nerve ablation. Data on noradrenaline spillover in this study correlated closely with the reduction in BP, and the authors suggest that renal International Journal of Hypertension sympathetic nerve ablation is a safe and eﬀective approach to the treatment of resistant hypertension. Long-term followup on patients undergoing renal sympathetic nerve denervation will be needed to determine the duration of beneﬁt and long- term safety of such an approach. 4. 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