title: Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.
abstract: Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Banek
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Mark M
authors.initials: MM
authors.lastname: Knuepfer
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Jason D
authors.initials: JD
authors.lastname: Foss
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Fiege
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Ninitha
authors.initials: N
authors.lastname: Asirvatham-Jeyaraj
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Dusty
authors.initials: D
authors.lastname: Van Helden
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.).
authors.forename: Yoji
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: From the Department of Integrative Biology and Physiology (C.T.B., J.D.F., N.A.-J., D.V.H., J.W.O.) and Department of Laboratory Medicine and Pathology (J.K.F., Y.S), University of Minnesota Medical School, Minneapolis; and Department of Pharmacology and Physiology, Saint Louis University School of Medicine, MO (M.M.K.). osbor003@umn.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Osborn
mesh_terms: D000818:Animals; D064791:Desoxycorticosterone Acetate / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D008297:Male; D009393:Nephritis / Q000503:physiopathology; D009475:Neurons, Afferent / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest; D012380:Role; D013562:Sympathectomy / Q000379:methods*; D013564:Sympathetic Nervous System / Q000503:physiopathology
chemical_list: D064791:Desoxycorticosterone Acetate
keywords: afferent neurons; arterial pressure; denervation; deoxycorticosterone acetate; hypertension; inflammation