Conclusion: Single Aliskiren treatment has renal and vascular protective effects in hypertensive patients with CKD. It inhibited plasma renin activity but did not affect serum s(P)RR levels in these patients. ERIGUCHI MASAHIRO, learn more TORISU KUMIKO, MASUTANI KOSUKE, TSURUYA KAZUHIKO, KITAZONO TAKANARI Department of Medicine and Clinical Science Graduate School of Medical Sciences, Kyushu University Introduction: Recently, catheter-based renal sympathetic denervation (DNx) has been applied in the clinical setting. Despite treatment with renin-angiotensin system (RAS) inhibitors and β-blockers for most

patients with DNx involved in these clinical studies, potential beneficial effects beyond blood pressure control have not been fully elucidated. The current study aimed to elucidate the underlying mechanisms of bidirectional

cardio-renal interaction, including the cycle involving the sympathetic nervous system (SNS) and RAS. We speculated that the mechanisms of the cardio-renal cycle may involve renal sympathetic nerves driving disruption of local RAS. Methods: A Wistar rat chronic Nω-nitro-L-arginine NVP-BKM120 methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration model was used to induce damage both in the heart and kidney, similar to cardio-renal syndrome. The rats were divided into four groups: control, L-NAME, L-NAME with bilateral DNx, and L-NAME with hydralazine group. Cardio-renal injury, SNS, circulating RAS and local RAS were evaluated. We also examined rats treated with L-NAME + unilateral DNx to confirm direct sympathetic regulation of intrarenal RAS. Serial measurements of kidney angiotensin II and urinary

angiotensinogen of both kidneys were performed to examine the laterality of local RAS within the same rats. Results: L-NAME induced SNS-RAS over-activity Org 27569 and cardio-renal injury accompanied by local RAS elevations. These changes were suppressed by bilateral DNx, but not by hydralazine treatment, even though blood pressure was kept to the same levels. Although L-NAME induced local RAS activation to similar levels in both organs, kidney angiotensinogen mRNA was suppressed contradictory; that was different from the heart with increasing in angiotensinogen mRNA. Immunostaining for angiotensinogen suggested that DNx suppressed local generation of angiotensinogen by activating macrophages/cardiac fibroblasts in the heart and circulatory angiotensinogen excretion from glomeruli of the kidney. In term of unilateral DNx model, the levels of kidney angiotensin II and urinary angiotensinogen from denervated kidneys were less than the levels from contralateral innervated kidneys within the same rats. Renal injury in denervated kidneys was alleviated compared with contralateral innervated kidneys by the end of the study.