title: Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease.
abstract: We elucidate the underlying mechanisms of bidirectional cardiorenal interaction, focusing on the sympathetic nerve driving disruption of the local renin-angiotensin system (RAS). A rat model of N(ω)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in the heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite the blood pressure being kept the same between the two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in the kidney and increased in the heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of the heart and circulating AGT excretion from glomeruli of the kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and the degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within the same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eriguchi
authors.affiliation: 1] Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan [2] Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Haruyama
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takaichi
authors.initials: T
authors.lastname: Suehiro
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masutani
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Torisu
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000818:Animals; D001794:Blood Pressure; D059347:Cardio-Renal Syndrome / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control*; D007668:Kidney / Q000294:innervation*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012084:Renin-Angiotensin System / Q000502:physiology; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology