title: The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension.
abstract: In the spontaneously hypertensive (SH) rat, hyperoxic inactivation of the carotid body (CB) produces a rapid and pronounced fall in both arterial pressure and renal sympathetic nerve activity (RSA). Here we show that CB de-afferentation through carotid sinus nerve denervation (CSD) reduces the overactive sympathetic activity in SH rats, providing an effective antihypertensive treatment. We demonstrate that CSD lowers RSA chronically and that this is accompanied by a depressor response in SH but not normotensive rats. The drop in blood pressure is not dependent on renal nerve integrity but mechanistically accompanied by a resetting of the RSA-baroreflex function curve, sensitization of the cardiac baroreflex, changes in renal excretory function and reduced T-lymphocyte infiltration. We further show that combined with renal denervation, CSD remains effective, producing a summative response indicative of an independent mechanism. Our findings indicate that CB de-afferentation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension.
authors.affiliation: School of Physiology and Pharmacology, Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, England.
authors.forename: Fiona D
authors.initials: FD
authors.lastname: McBryde
authors.forename: Ana P
authors.initials: AP
authors.lastname: Abdala
authors.forename: Emma B
authors.initials: EB
authors.lastname: Hendy
authors.forename: Wioletta
authors.initials: W
authors.lastname: Pijacka
authors.forename: Paul
authors.initials: P
authors.lastname: Marvar
authors.forename: Davi J A
authors.initials: DJ
authors.lastname: Moraes
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sobotka
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000502:physiology*; D017704:Baroreflex / Q000502:physiology; D002344:Carotid Body / Q000378:metabolism / Q000601:surgery; D002346:Carotid Sinus / Q000294:innervation* / Q000601:surgery*; D002465:Cell Movement / Q000276:immunology; D003714:Denervation; D006321:Heart / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000628:therapy*; D007668:Kidney / Q000294:innervation / Q000601:surgery; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000601:surgery*; D013601:T-Lymphocytes / Q000276:immunology